[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"recurrent-glioblastoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:recurrent-glioblastoma":29},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,46,0,25,[9,49,76,105,129,153,176,198,237,264,284,312,343,365,388,411,433,464,493,519,542,570,596,628,652],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":16,"eligibilityCriteria":17,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":31,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100508572","phase-3-sonocloud-9-in-association-with-carboplatin-versus-standard-of-care-chemotherapies-ccnu-or-tmz-in-recurrent-gbm-100508572",false,"NCT05902169","Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM","A Randomized, Open-label, Multicentric, Two-arm Pivotal Trial of SonoCloud-9 Combined With Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) or Temozolomide (TMZ) in Patients Undergoing Planned Resection for First Recurrence Glioblastoma.","SONOBIRD","Inclusion Criteria:\n\n1. Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.\n2. Patient must have received prior first line therapy that must have contained both:\n\n   1. Prior surgery or biopsy and standard fractionated radiotherapy (1.8-2 Gy\u002Ffraction, ≥56 Gy\\\u003C66 Gy) or hypofractionated radiotherapy (15 x 2.66 Gy or similar regimen)\n   2. One line of maintenance chemotherapy and\u002For immune- or biological therapy, (with or without Tumor-Treating Fields)\n3. First, unequivocal disease progression with\n\n   1. measurable tumor (\\>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI and,\n   2. interval of a minimum of 12 weeks since the completion of prior radiotherapy, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling\n4. Patient is a candidate for craniotomy and at least 50% resection of enhancing region\n5. Maximal enhancing tumor diameter prior to inclusion ≤ 5 (+7%) cm on T1w on MRI performed within 14 days prior to inclusion§. (In case of planned lobectomy, post operative peritumoral brain or residual size ≤5 cm)\n6. WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70)\n7. Age ≥ 18 years\n8. Participant must be recovered from acute toxic effects (≤ grade 2) of all prior anticancer therapy. Interval since last therapy to presumed date of surgery of at least:\n\n   1. ≥ 4 weeks or 5 half-lives (whichever is shorter) for\n\n      * Cytotoxic\n      * Other small chemical entity (e.g., targeted therapy)\n      * For biologics (e.g., antibodies, except bevacizumab)\n   2. ≥ 6 weeks of prior bevacizumab\n9. Adequate hematologic, hepatic, and renal laboratory values within 14 days prior to inclusion§ i.e.:\n\n   1. Hemoglobin ≥ 10 g\u002FdL, platelets ≥ 100,000\u002Fmm3, neutrophils ≥ 1500\u002Fmm3.\n   2. Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome\n   3. Estimated glomerular filtration rate (eGFR) of at least 60 mL\u002Fmin\u002Fm2 using Appendix 12.4 formula\n   4. AST(SGOT)\u002FALT(SPGT) ≤ 3 X institutional ULN (upper Limit of Normal)\n10. Patient able to understand clinical trial information and willing to provide signed and informed consent\n11. Patient of childbearing potential must have a negative pregnancy test within 14 days prior to inclusion§ and must agree to use a medically-acceptable method of birth control during the treatment period and, if randomized in the experimental arm, for at least 1 month after the last cycle of carboplatin\n12. A male patient must agree to use condoms during the treatment period and, if randomized in the experimental arm, for at least 3 months after the last cycle of carboplatin; the patient must also refrain from donating sperm during this period.\n13. Patient must be a beneficiary of a health plan that covers routine patient care costs. Patient must be a beneficiary of or affiliated with a social security scheme (according to country-specific requirements)\n\n(§) These exam\u002Flab tests could be (re)evaluated before randomization if the corresponding selection criteria could not be fully met at time of inclusion. If not met before randomization, the patient will be considered as screen failure.\n\nNon-Inclusion Criteria:\n\n1. Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area)\n2. Posterior fossa tumor\n3. Known BRAF\u002F NTKR mutated patients\n4. Patient at risk of surgery site infection (e.g., 2 or more previous craniotomies\u002Fneurosurgery within the last 3 months, poor skin condition, known impaired wound healing and\u002For previously infected surgical field, uncontrolled diabetes or any other condition that is of increased infectious risk in the opinion of the neurosurgeon)\n5. Patient treated at high, stable -or average- dose of corticosteroids (≥ 6 mg\u002Fday dexamethasone or equivalent) in the 7 days prior to inclusion. Patients on dexamethasone for reasons other than mass effect may still be enrolled.\n6. Contra-indication to carboplatin, CCNU or TMZ\n7. Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator\n8. Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema\n9. Peripheral neuropathy or neuropathy ≥ grade 2\n10. Uncontrolled epilepsy or evidence of intracranial pressure\n11. Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage\n12. Patient with unremovable coils, clips, shunts, intravascular stents, and\u002For wafer, or reservoirs\n13. Patient with medical need to be on continued anti-platelet aggregation therapy and\u002For anticoagulation. Patients for whom anticoagulation\u002Fplatelet aggregation can be temporarily interrupted may be eligible after discussion and prior authorization by the sponsor.\n14. Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen\n15. History of other malignancy within 3 years prior to study start with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma, non-melanomatous skin cancer or carcinoma in situ of the uterine cervix\n16. Patient with known or suspected active or chronic infections\n17. Patient with known significant cardiac disease, known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure \\> 90 mm Hg), uncontrolled systemic hypertension, or acute respiratory distress syndrome\n18. Known sensitivity\u002Fallergy to gadolinium, or other intravascular contrast agents\n19. Patient with impaired thermo-regulation or temperature sensation\n20. Pregnant, or breastfeeding patient\n21. Any other serious patient medical or psychological condition that may interfere with adequate and safe delivery of treatment and care (e.g., positive human immunodeficiency virus \\[HIV\\] status, potential blood-borne infections, malnutrition…), circumstance (e.g., sinus opening during surgery), psychological, morphological characteristics (e.g., skin characteristics, bone thickness), or any pre-existing comorbidities that in the investigator's opinion may prevent the implantation of the device, may impair the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical trial endpoints\n22. Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision\n\nExclusion Criterion:\n\nOccurrence of any major medical illnesses or impairments that in the Investigator's opinion may hampered the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical endpoints.","ALL","18 Years",{"count":21,"type":22},560,"ESTIMATED","INTERVENTIONAL",[25],"PHASE3","The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. The development of effective treatments against glioblastoma is thus limited due to the BBB that prevents most drugs injected in the bloodstream from getting into brain tissue where the tumour is seated. The SonoCloud-9 (SC9) is an investigational device using ultrasound technology and specially developed to open the BBB in the area of and surrounding the tumour. The transient opening of the BBB allows more drugs to reach the brain tumour tissue. Carboplatin is a chemotherapy that is approved to treat different cancer types alone or in combination with other drugs, and has been used in the treatment of glioblastoma. Despite its proven efficacy in the laboratory on glioblastoma cells, carboplatin does not readily cross the BBB in humans. A clinical trial has shown that in combination with the SonoCloud-9, more carboplatin can reach the brain tumour tissue. The objective of the proposed trial is to show that the association - carboplatin with the SonoCloud-9 - will increase efficacy of the drug in patients with recurrent glioblastoma.",[28,29,30],"Glioblastoma","Recurrent Glioblastoma","GBM",[32,33,34,35],"carboplatin","SonoCloud","blood-brain barrier","Low Intensity Pulsed Ultrasound (LIPU)","RECRUITING","2026-08-17",{"date":39,"type":40},"2026-08-18","ACTUAL",{"date":42,"type":40},"2024-01-29",{"date":44,"type":22},"2028-06-30",{"name":46,"class":47},"CarThera","INDUSTRY",55,{"id":50,"slug":51,"hasResults":12,"nctId":52,"briefTitle":53,"officialTitle":54,"acronym":55,"eligibilityCriteria":56,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":57,"targetDuration":4,"studyType":23,"phases":59,"briefSummary":61,"conditions":62,"keywords":64,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":68,"startDateStruct":69,"completionDateStruct":70,"leadSponsor":72,"locationsCount":75},"100431875","phase-1-brite---bispecific-t-cell-engager-for-patients-with-glioblastoma-100431875","NCT04903795","BRiTE - Bispecific T Cell Engager for Patients With Glioblastoma","A Phase 1 Study of Bispecific T Cell Engager (BRiTE) in Patients With Newly Diagnosed or Recurrent Glioblastoma","BRiTE","Inclusion Criteria:\n\n1. Age ≥ 18 years old at the time of entry into the study\n2. For both newly diagnosed and recurrent patients, pathologically documented supratentorial WHO grade 4 GBM with a confirmed EGFRvIII mutation at the most recent diagnosis, with radiographic contrast enhancing disease that is ≤ 4 cm in maximal diameter in any plane before resection.\n\n   i. ndGBM patients: Must have undergone surgical resection of their tumor. Patients are still eligible if they have measurable or non-measurable residual enhancing tumor following resection, providing they meet all other eligibility criteria. Newly diagnosed patients must complete standard of care RT with or without TMZ before participation, depending on the MGMT promoter methylation status as follows:\n   1. Patients with methylated MGMT promoter status should have received standard of care concomitant RT and TMZ, followed by 6 cycles of adjuvant TMZ, before they can participate in this study\n   2. Patients with an unmethylated MGMT promoter status should have received standard of care RT, but need not have received concomitant TMZ or 6 cycles of adjuvant TMZ and can be enrolled after 4 weeks from completion of standard of care RT\n   3. Patients whose MGMT status is unknown or indeterminate will be treated as though they have a methylated MGMT promotor status for eligibility purposes\n   4. RT for 3 or 6-week courses are accepted as follows:\n\n      * Typically, 59.4-60 Gy over approximately 6 weeks duration, if under 65 years old\n      * A minimum of 40 Gy over 3 weeks duration, if 65 years or older\n   5. Patients who progress during RT or within 4 weeks after completion of RT are not eligible.\n\n   ii. rGBM patients at first progression: Must have pathological or radiographic confirmation of their tumor recurrence that is ≤ 4 cm in maximal diameter in any plane.\n\n   Note: Patients that undergo total gross resection at time of recurrence are eligible to enroll. Patients are still eligible if they have measurable or non-measurable residual enhancing tumor following resection, providing they meet all other eligibility criteria.\n3. Karnofsky Performance Score (KPS) ≥ 70%\n4. Able to undergo brain MRI with and without contrast. Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (i.e. pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates) or patients with any known severe allergies to contrast agents are not eligible. Patients with mild allergies (i.e., rash only) are eligible for inclusion and can be pretreated with acetaminophen and diphenhydramine prior to injection of the contrast agent.\n5. Hematological function as follows:\n\n   i. Hemoglobin ≥ 9.0 g\u002FdL ii. Absolute neutrophil count (ANC) ≥ 750\u002Fmm3 iii. Platelet count ≥ 50,000\n6. Renal function as follows:\n\n   i. Creatinine ≤ 1.5 x ULN\n7. Hepatic function as follows:\n\n   i. Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) ii. Alanine aminotransferase (ALT) ≤ 2.5 x ULN iii. Total bilirubin ≤ 1.5 x ULN Exception: Patient has known Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional lab testing of direct and\u002For indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.\n8. Patient or partner(s) meets one of the following criteria:\n\n   1. Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any person who is post-menopausal or surgically sterile, or any person who has had a vasectomy). Surgically sterile people are defined as those with a documented hysterectomy and\u002For bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses; or\n   2. Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide while on study and for an additional 4 months after completing the last infusion of BRiTE.\n9. Patients of childbearing potential must have negative serum pregnancy test within 1 week of the 1st BRiTE infusion\n10. A signed ICF approved by the IRB will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study. Patient must also agree that a caregiver will accompany them for the Day 4 (96 hours) clinic visit during every cycle of BRiTE and be present with them for 24 hours after the end of the infusion.\n\nExclusion Criteria for All Patients:\n\n1. Patients who are pregnant or breastfeeding\u002Fchestfeeding\n2. Patients with baseline corrected QT interval (QTc) \\> 480ms on screening electrocardiogram (ECG).\n\n   Note: QTc measurements will use Fridericia's correction method (QTcF).\n3. Known hypersensitivity to immunoglobulins or to any other component of BRiTE\n4. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate\n5. Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin\n6. Patients with severe, active co-morbidity, defined as follows:\n\n   i. Patients with an active infection requiring IV treatment or having an unexplained febrile illness (Tmax \\> 99.5°F\u002F37.5°C) ii. Patients with known immunosuppressive disease or known HIV infection, with CD4+ T cell counts \\\u003C 350 cells\u002Fµl iii. Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4) iv. Patients with known lung (forced expiratory volume in the first second of expiration \\[FEV1\\] \\\u003C 50%) disease or uncontrolled diabetes mellitus v. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy\n7. Patients with known Human Immunodeficiency Virus (HIV) positive status only if CD4+ T cell counts \\\u003C 350 cells\u002Fµl. Patients with known HIV and CD4+ T cell counts over 350 cells\u002Fµl are eligible.\n8. Patients with known hepatitis C virus (HCV) positive status, who have not completed curative antiviral treatment and have HCV viral load above the limit of quantification. Patients with well-controlled HCV are eligible.\n9. Patients with known hepatitis B virus (HBV) infection, with evidence of a hepatitis B surface antigen, indicative of an active infection. Patients with well-controlled HBV are eligible.\n10. Patients on corticosteroids ≥ 2 mg dexamethasone daily or equivalent within 7 days of 1st BRiTE infusion\n11. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months\n12. Toxicities from prior antitumor therapy that have not resolved to CTCAE version 5.0 grade 1 (with the exception of AEs reflecting myelosuppression such as neutropenia, anemia, or thrombocytopenia), or to levels dictated in the eligibility criteria. Other exceptions include alopecia or toxicities from prior antitumor therapy that are considered irreversible (defined as having been present and stable for \\> 2 months) are allowed if they are not otherwise described in the exclusion criteria.\n\nExclusion Criteria for ndGBM Patients Only:\n\n1. Patients who previously received other therapeutic interventions for ndGBM, with the exception of surgical resection and standard of care concomitant RT and TMZ (including adjuvant TMZ) for their brain tumor\n2. Patients who have had only a biopsy prior to receiving standard of care concomitant RT and TMZ\n3. Unmethylated MGMT patients who have received RT \\\u003C 4 weeks prior to initiation of BRiTE infusion\n\nExclusion Criteria for rGBM Patients Only:\n\n1. Patients who have received chemotherapy or bevacizumab ≤ 4 weeks \\[except for nitrosourea (6 weeks), or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)\\] prior to enrollment unless patients have recovered from side effects of such therapy\n2. Patients who have received immunotherapy prior to enrollment\n3. Patients less than 12 weeks from RT, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation prior to enrollment",{"count":58,"type":22},18,[60],"PHASE1","This Phase 1 study will assess the safety of a novel brain Bispecific T cell engager (BRiTE) in patients with newly diagnosed or recurrent World Health Organization (WHO) Grade 4 glioblastoma (GBM). Owing to its short half-life, the study drug, BRiTE, will be continuously infused intravenously (IV) for 4 days (96 hours) in a 28-day cycle. Given that BRiTE specifically exerts its effects on tumor cells expressing the Epidermal Growth Factor Receptor variant III (EGFRvIII) mutation, we will only enroll patients with EGFRvIII-positive tumors in this study.\n\nThe primary objective is to evaluate the safety and tolerability of continually infused BRiTE in ndGBM and rGBM patients and determine the maximum tolerated dose (MTD) for continuously infused BRiTE.",[63,29],"Newly Diagnosed Glioblastoma",[65,66,55,67],"EGFRvIII","Khasraw","Pro00108079",{"date":39,"type":40},{"date":37,"type":40},{"date":71,"type":22},"2027-12-30",{"name":73,"class":74},"Mustafa Khasraw, MBChB, MD, FRCP, FRACP","OTHER",1,{"id":77,"slug":78,"hasResults":12,"nctId":79,"briefTitle":80,"officialTitle":81,"acronym":4,"eligibilityCriteria":82,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":83,"enrollmentInfo":84,"targetDuration":4,"studyType":23,"phases":86,"briefSummary":87,"conditions":88,"keywords":91,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":95,"lastUpdatePostDateStruct":96,"startDateStruct":98,"completionDateStruct":100,"leadSponsor":102,"locationsCount":75},"100542535","phase-1-hypofractionation-trial-of-re-irradiation-in-good-prognosis-recurrent-glioblastoma-100542535","NCT06344130","Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma","A Phase I Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma","* INCLUSION CRITERIA:\n* Histologic diagnosis of primary glioblastoma or gliosarcoma of the brain, or secondary glioblastoma of the brain due to transformation from a lower grade to a grade 4 tumor.\n* Age \\>= 18.\n* KPS \\>= 70%.\n* Previous tumor irradiation to curative-intent doses.\n* Radiation dose constraints must be achievable based on assessment with MRI and treatment planning CT.\n* Participants must have adequate organ and marrow function as defined below:\n\n  * Absolute neutrophil count (ANC) \\>= 1,000\u002FmicroL\n  * Platelets \\>= 100,000\u002FmicroL\n* Individuals of child-bearing potential (IOCBP) and individuals who can father children must agree to use effective contraception (barrier, hormonal, intrauterine device, surgical sterilization, abstinence) from study entry and through 6 months after the last study treatment (restricted period). Individuals who can father children must not freeze or donate sperm within the same period.\n* Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last study treatment.\n* The ability of a participant to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Recent systemic therapy prior to the initiation of the study therapy as follows:\n\n  * Bevacizumab used for reasons other than tumor progression or symptomatic management within 2 weeks.\n  * Temozolomide within 2 weeks.\n  * Cytotoxic chemotherapy within 3 weeks.\n  * Any investigational agents within 2 weeks.\n* Participants who are unable to undergo MRI evaluation or receive gadolinium contrast for any reason.\n* Any prior therapy after surgical re-resection or biopsy within 2 weeks prior to the initiation of the study therapy.\n* Requiring radiation therapy within 12 months prior to the initiation of study therapy.\n* History of prior therapy with Novacure TTF, Gliadel wafers, or GammaTile therapy.\n* Positive beta-human chorionic gonadotropin (HCG) pregnancy test performed in individuals of childbearing potential at screening.\n* Participants with known or suspected radiation sensitivity syndromes.\n* Uncontrolled intercurrent illness evaluated by medical history and physical exam that are not stable and would potentially increase the risk to the participant.","120 Years",{"count":85,"type":22},28,[60],"Background:\n\nGlioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. No standard treatment exists for people whose GBM has returned after radiation therapy.\n\nObjective:\n\nTo find a safe schedule for using radiation to treat GBM tumors that returned after initial radiation treatment.\n\nEligibility:\n\nPeople aged 18 years and older with grade 4 GBM that returned after initial radiation treatment.\n\nDesign:\n\nParticipants will be screened. They will have a physical exam with blood tests. A sample of tumor tissue may be collected.\n\nParticipants will undergo re-irradiation planning: They will wear a plastic mask over their head during imaging scans. These scans will pinpoint the exact location of the tumor. This spot will be the target of the radiation treatments.\n\nParticipants will undergo radiation treatment 4 times per week. Some people will have this treatment for 3 weeks, some for 2 weeks, and some for 1 week. Blood tests and other exams will be repeated at each visit.\n\nParticipants will complete questionnaires about their physical and mental health. They will answer these questions before starting radiation treatment; once a week during treatment; and at intervals for up to 3 years after treatment ends.\n\nParticipants will have follow-up visits 1 month after treatment and then every 2 months for 6 months. Follow-up clinic visits will continue up to 3 years. Follow-ups by phone or email will continue an additional 2 years.",[89,90,29],"Astrocytoma","Glioma",[92,93,94],"Radiotherapy","Hypofractionation","Re-irradiation","2026-08-13",{"date":97,"type":40},"2026-08-14",{"date":99,"type":40},"2024-10-01",{"date":101,"type":22},"2027-12-31",{"name":103,"class":104},"National Cancer Institute (NCI)","NIH",{"id":106,"slug":107,"hasResults":12,"nctId":108,"briefTitle":109,"officialTitle":110,"acronym":4,"eligibilityCriteria":111,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":112,"targetDuration":4,"studyType":23,"phases":114,"briefSummary":115,"conditions":116,"keywords":119,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":122,"lastUpdatePostDateStruct":123,"startDateStruct":124,"completionDateStruct":126,"leadSponsor":127,"locationsCount":75},"100530409","phase-1-anti-egfrviii-synnotch-receptor-induced-anti-epha2il-13ralpha2-car-e-sync-t-cells-100530409","NCT06186401","Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2\u002FIL-13Ralpha2 CAR (E-SYNC) T Cells","Phase 1 Study of Autologous Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2\u002FIL-13R alpha2 CAR (E-SYNC) T Cells in Adult Participants With EGFRvIII+ Glioblastoma","Inclusion Criteria:\n\n* Inclusion Criteria for Cohort 1:\n\n  1. Age \\>= 18 years.\n  2. Karnofsky performance status (KPS) score of \\>=70.\n  3. All participants must have adequate organ function defined as:\n\n     1. Peripheral absolute neutrophil count \\>=1000\u002Fmm\\^3.\n     2. Platelet count \\>=100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n     3. Absolute lymphocyte count (ALC) \\>= 300\u002FμL and\u002For Cluster of differentiation 3 (CD3) count of \\>=150\u002FμL.\n     4. Creatinine clearance or radioisotope glomerular filtration rate \\>= 50 mL\u002Fmin\u002F1.73m\\^2.\n     5. Total Bilirubin \\\u003C= 1.5 x ULN except for Gilbert's syndrome and\n     6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 3x upper limit of normal (ULN).\n     7. Left ventricular ejection fraction (LVEF) \\>= 50% by echocardiogram or multi-gated acquisition scanning (MUGA).\n     8. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n  4. Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel.\n  5. MGMT promoter must be unmethylated or with a methylation index \\\u003C 3.\n  6. Must have completed at least standard of care (SOC) external beam radiotherapy (EBRT) as initial therapy.\n  7. Participants must be anticipated to be able to complete E-SYNC T cell infusion within 12 weeks after completion of EBRT.\n  8. All participants must be off systemic steroids for 3 days or more prior to leukapheresis.\n  9. Must be willing to provide voluntary informed consent for apheresis (and tissue screening if needed) and for study treatment.\n\nNOTE: There are two sets of eligibility criteria for Cohort 2. Tissue Screening: Defines eligibility for tissue screening and to determine H-score.\n\nStudy Enrollment: Defines eligibility for study enrollment and E-SYNC T cell manufacturing\u002Ftreatment.\n\n* Inclusion Criteria for Tissue Screening Cohort 2:\n\n  1. Age \\>=18 years.\n  2. Pathological criteria: EGFRvIII+ GBM from most recent surgery, confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab using a next-generation sequencing panel.\n* Inclusion Criteria for Study Enrollment for Cohort 2\n\n  1. Karnofsky Performance Scale (KPS) score \\>=70.\n  2. received at least standard of care external beam radiotherapy (SOC EBRT) as initial therapy, with or without concurrent temozolomide (TMZ), and completed the last dose of TMZ ≥23 days prior to study enrollment). Note: patients may have initiated adjuvant TMZ +\u002F- TTFields.\n  3. Pathological criteria: EGFRvIII+ GBM from most recent surgery, as defined by an EGFRvIII H-score of ≥ 150 based on central review.\n  4. Is surgically amenable, with expectation for ability to resect at least 500 mg of tumor tissue confirmed by participant's neurosurgeon.\n  5. Participants with reproductive potential agree to use reliable and double barrier method of contraception during the study and for at least 6 months after the last study intervention, including refraining from donating sperm during this period.\n  6. Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test prior to receiving study interventions.\n  7. All participants must have adequate organ function.\n\n     a. Adequate bone marrow function is defined as: i. Peripheral absolute neutrophil account ≥ 1000\u002Fmm3 and ii. Platelet count ≥ 100,000\u002Fmm3 (transfusion dependent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) and iii. Absolute lymphocyte count (ALC) ≥ 300\u002FµL and\u002For CD3 count of ≥ 150\u002FµL b. Adequate renal function is defined as: i. Creatinine clearance or radioisotope glomerular filtration rate ≥ 50 mL\u002Fmin\u002F1.73m2 c. Adequate liver function is defined as: i. Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) except for Gilbert's syndrome and ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN d. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the participant has been therapeutically anti-coagulated for previous venous thrombosis. e. Adequate pulmonary function, defined as no evidence of dyspnea at rest and pulse oximetry \\> 92% while breathing room air.\n\n     f. Adequate cardiac function, confirmed within the last 12 months, defined as: i. Left ventricular ejection fraction (LVEF) ≥ 40% by echocardiogram or multi-gated acquisition scanning (MUGA)\n  8. Must be willing to provide voluntary informed consent for study intervention.\n\nExclusion Criteria:\n\n* Exclusion Criteria for Cohort 1\n\n  1. Participant who has been treated with any investigational agents and chemotherapy targeting GBM \\\u003C= 4 weeks prior to date of study registration. Exceptions to this include: must be \\>=23 days from last dose of temozolomide (TMZ) or radiotherapy, mush be \\>= 6 weeks from last dose of nitrosourea.\n  2. Female participants of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of eligibility confirmation.\n  3. Known addiction to alcohol or illicit drugs.\n  4. Prior treatment with any Epithelial Growth Factor Receptor (EGFR)-targeting therapy.\n  5. Participants with leptomeningeal dissemination.\n  6. Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy. Participants who are currently using non-systemic steroids (e.g., inhaled, intranasal, ocular, topical) are not excluded from the study.\n  7. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n  8. Participants who have received prior solid organ or bone marrow transplantation.\n  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, second cancer currently receiving active treatment or anticipated to receive treatment within the next year, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n  10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.\n* Exclusion Criteria for Tissue Screening for Cohort 2\n\n  1\\. Participant is unwilling to undergo another surgery if felt clinically appropriate.\n* Exclusion Criteria for Study Enrollment for Cohort 2\n\n  1. Prior treatment with any EGFR-targeting therapy\n  2. Participant who has been treated with any investigational agents, chemotherapy, or biological therapy targeting GBM \\\u003C= 4 weeks prior to date of study registration. Exceptions to this include: no TMZ \\\u003C= 23 days or nitrosourea \\\u003C= 6 weeks prior to study enrollment. There is no washout prior to study enrollment for TTFields, but use of the device must be stopped at least 1 week prior to initiation of lymphodepleting (LD) chemotherapy.\n  3. Participants with imaging or clinical evidence of uncontrolled tumor mass effect; the assessment of mass effect will be made by the Investigators.\n  4. Participants with leptomeningeal dissemination.\n  5. Participants with a known disorder that affects their immune system, such as HIV or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy.\n\n     Participants who are currently using inhaled, intranasal, ocular, topical, or other non-oral or non-IV steroids are not necessarily excluded from the study.\n  6. Participants with serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B surface antigen (HBsAg+) will be excluded. Participants that are positive for hepatitis B core antibody or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive participants will be excluded.\n  7. Participants who have received prior solid organ or bone marrow transplantation.\n  8. Female participants who are pregnant or breast-feeding.\n  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, second cancer currently receiving active treatment or anticipated to receive treatment within the next year, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n  10. Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.",{"count":113,"type":22},20,[60],"This phase I trial tests the safety, side effects, and best dose of E-SYNC chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy in treating patients with EGFRvIII positive (+) glioblastoma. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so the CAR T cells will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine before treatment with CAR T cells may make the CAR T cells more effective.",[117,28,118,29],"EGFR Gene Mutation","MGMT-Unmethylated Glioblastoma",[120,121],"Immunotherapy","CAR T Therapy","2026-08-11",{"date":95,"type":40},{"date":125,"type":40},"2024-04-30",{"date":101,"type":22},{"name":128,"class":74},"Hideho Okada, MD, PhD",{"id":130,"slug":131,"hasResults":12,"nctId":132,"briefTitle":133,"officialTitle":134,"acronym":4,"eligibilityCriteria":135,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":136,"targetDuration":4,"studyType":23,"phases":138,"briefSummary":140,"conditions":141,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":143,"lastUpdatePostDateStruct":144,"startDateStruct":146,"completionDateStruct":148,"leadSponsor":150,"locationsCount":152},"100598689","a-digital-treatment-platform-for-the-delivery-of-home-based-sequential-therapy-in-patients-with-glioma-ghost-trial-100598689","NCT07074756","A Digital Treatment Platform for the Delivery of Home-Based Sequential Therapy in Patients With Glioma, GHoST Trial","MC240703 Neuro-Oncology Anywhere: Glioma Home-Based Sequential Therapy (GHoST) Protocol","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Diagnosis of glioma and intention to treat with either new or ongoing systemic therapy for at least 6 months.\n\n  * NOTE: Patient may be enrolled following completion of surgery and\u002For radiation therapy for newly diagnosed or recurrent tumor.\n  * NOTE: Any number of prior recurrences is permitted\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, AND Karnofsky performance status (KPS) of ≥ 60\n* Expected survival ≥ 6 months in the opinion of treatment team\n* Willing and able to adhere with the protocol for the duration of the study including undergoing treatment, and attending scheduled visits, and examinations\n* Negative pregnancy test ≤ 8 days prior to registration for persons of childbearing potential only\n\n  * Exception: Not required if patient is already on treatment. May be obtained prior to next treatment as needed per clinical care\n* Provide written informed consent\n* Ability to complete assessments and questionnaires by themselves or with assistance\n* SUBSTUDY 1: Enrolled in GHoST Master Protocol per eligibility criteria of the master study and clinically appropriate to proceed with bevacizumab treatment at the discretion of the treating physician\n* SUBSTUDY 1: Diagnosis of recurrent glioblastoma and intention to treat with bevacizumab\n\n  * NOTE: Any number of prior recurrences is permitted\n  * NOTE: Prior limited use of bevacizumab for radiation necrosis\u002Ftreatment related edema is permitted. Prior use should not exceed four infusions with the last dose administered ≥ 4 weeks prior to enrollment in this substudy\n* SUBSTUDY 1: Willing and able to adhere to the substudy for the duration of the substudy including undergoing treatment, and attending scheduled visits, and examinations\n* SUBSTUDY 1: Negative pregnancy test ≤ 8 days prior to registration for persons of childbearing potential only\n* SUBSTUDY 1: Provide written informed consent\n* SUBSTUDY 1: Ability to complete assessments and questionnaires by themselves or with assistance\n\nExclusion Criteria:\n\n* Pregnant or nursing, imprisoned, or lacking capacity for understanding\n* Uncontrolled and\u002For intercurrent illness or other condition which limits safety of or compliance with study proceedings\n* SUBSTUDY 1: Pregnant or nursing, imprisoned, or lacking capacity for understanding\n* SUBSTUDY 1: Uncontrolled and\u002For intercurrent illness or other condition which limits safety of or compliance with study proceedings",{"count":137,"type":22},202,[139],"NA","This clinical trial tests how well a digital treatment platform using a mobile application works for the delivery of home-based sequential therapy in patients with glioma. Access to specialized neuro-oncology care in the United States for patients with glioma is critically deficient. Care at centers with neuro-oncology specialists is associated with improved survival outcomes, yet many patients have limited access due to distance, disease-related disability, or lack of financial resources. The application provides patients continuous access to their care team in the home setting. A digital treatment platform may increase clinical trial participation and accelerate development of novel therapeutics while addressing a great health disparity in patients with glioma.",[90,142,29],"Recurrent Glioma","2026-08-06",{"date":145,"type":40},"2026-08-10",{"date":147,"type":40},"2025-09-12",{"date":149,"type":22},"2028-08-31",{"name":151,"class":74},"Mayo Clinic",2,{"id":154,"slug":155,"hasResults":12,"nctId":156,"briefTitle":157,"officialTitle":157,"acronym":158,"eligibilityCriteria":159,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":160,"targetDuration":4,"studyType":23,"phases":162,"briefSummary":164,"conditions":165,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":166,"lastUpdatePostDateStruct":167,"startDateStruct":169,"completionDateStruct":171,"leadSponsor":173,"locationsCount":175},"100521448","phase-2-a-multicenter-trial-to-identify-optimal-atezolizumab-biomarkers-in-the-setting-of-recurrent-glioblastoma-the-moab-trial-100521448","NCT06069726","A Multicenter Trial to Identify Optimal Atezolizumab Biomarkers in the Setting of Recurrent Glioblastoma. The MOAB Trial","MOAB","Inclusion Criteria:\n\n1. Age ≥ 18 years old\n2. Pathologically confirmed GBM, IDHwt\n3. Clinical or radiologic evidence of first or second recurrence following radiation and TMZ. Note: A diagnostic biopsy is required prior to the commencement of the study drug if there is uncertainty about the MRI findings being true progression versus pseudoprogression.\n4. Tissue available from initial diagnosis of primary GBM\n5. Adequate organ function:\n\n   1. Hemoglobin ≥ 9 g\u002Fdl\n   2. Platelet count ≥ 75,000\u002Fµl\n   3. Neutrophil count ≥ 1000 cells\u002Fmm3\n   4. Creatinine ≤ 1.5 x ULN (calculated using the Cockcroft-Gault formula)\n   5. Total bilirubin ≤ 1.5 x ULN (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and\u002For indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)\n   6. Alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN)\n   7. AST and ALT ≤ 2.5 x ULN\n   8. Serum albumin ≥ 25 g\u002FL (2.5 g\u002FdL)\n   9. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x ULN\n6. Karnofsky Performance Status (KPS) ≥ 70%\n7. Patient or partner(s) meets one of the following criteria:\n\n   1. Non-childbearing potential (i.e., not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and\u002For bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or\n   2. Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g., birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g., a condom or diaphragm) used with spermicide.\n8. A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study.\n9. Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count \\> 200\u002FµL, and have an undetectable viral load\n10. Negative hepatitis B surface antigen (HBsAg) test at screening. Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening Note: The HBV DNA test will be performed only for patients who have a negative HBsAg test and a positive total HBcAb test.\n11. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening Note: The HCV RNA test must be performed for patients who have a positive HCV antibody test.\n\nExclusion Criteria:\n\n1. Pregnancy or breastfeeding or intention of becoming pregnant during study treatment or within 5 months of final dose of atezolizumab therapy\n\n   a) For women of childbearing potential: Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods as defined below: i) Women must remain abstinent or use contraceptive methods with a failure rate of \\\u003C 1% per year during the treatment period and for 5 months after the final dose of atezolizumab. Examples of contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.\n\n   ii) A woman is of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes and\u002For uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.\n\n   b) For men with pregnant female partners and\u002For with female partners of childbearing potential: Agree to remain abstinent (refrain from heterosexual intercourse) or use a condom and refrain from donating sperm.\n\n   i) With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period for 5 months after the final dose of atezolizumab to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.\n2. Prior treatment with immunotherapy\n3. Prior treatment with bevacizumab within 4 weeks before biopsy. Note: Bevacizumab will be permitted if necessary to control inflammatory side effects 5-7mg\u002Fkg Q 3\u002F52 for up to 3 cycles\n4. Treatment with systemic immunosuppressive medication (including, but not limited to, more than 2 mg of dexamethasone or equivalent corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:\n\n   1. Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.\n   2. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.\n5. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n6. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation\n7. Active autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix E in Section 16.5 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:\n\n   1. Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.\n   2. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.\n   3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:\n\n   i) Rash must cover \\\u003C 10% of body surface area ii) Disease is well controlled at baseline and requires only low-potency topical corticosteroids iii) There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.\n8. \\\u003C 12 weeks from radiation therapy, unless progressive disease outside of previous radiation field or 2 progressive MRIs, 4 weeks apart; (to avoid enrolling patients with pseudoprogression)\n9. Contraindication to surgery\n10. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina\n11. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study\n12. History of malignancy within 12 months prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \\> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage 1 uterine cancer.\n13. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety\n14. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab\n15. Treatment with investigational therapy within 28 days prior to initiation of study treatment\n16. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies\n17. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed.\n18. Uncontrolled or symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL or corrected serum calcium \\> ULN)\n19. Active tuberculosis\n20. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.\n21. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.\n22. Prior allogeneic stem cell or solid organ transplantation",{"count":161,"type":22},80,[163],"PHASE2","This is to study if neoadjuvant atezolizumab therapy is beneficial for patients with recurrent glioblastoma and a low mutational burden.",[29],"2026-07-30",{"date":168,"type":40},"2026-07-31",{"date":170,"type":40},"2024-03-21",{"date":172,"type":22},"2028-01-01",{"name":174,"class":74},"Duke University",4,{"id":177,"slug":178,"hasResults":12,"nctId":179,"briefTitle":180,"officialTitle":181,"acronym":182,"eligibilityCriteria":183,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":184,"targetDuration":4,"studyType":23,"phases":186,"briefSummary":187,"conditions":188,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":166,"lastUpdatePostDateStruct":190,"startDateStruct":191,"completionDateStruct":193,"leadSponsor":195,"locationsCount":197},"100462576","phase-1-a-feasibility-study-to-evaluate-the-safety-of-the-therasphere-glioblastoma-gbm-device-in-patients-with-recurrent-gbm-100462576","NCT05303467","A Feasibility Study to Evaluate the Safety of the TheraSphere Glioblastoma (GBM) Device in Patients With Recurrent GBM","FRONTIER: A Feasibility Study to Evaluate the Safety of the TheRaSphere GliOblastoma (GBM) Device iN PaTIEnts With Recurrent GBM","FRONTIER","Inclusion Criteria:\n\n1. Subject is 18 years or older and has signed and dated the trial informed consent form (ICF)\n2. Life expectancy ≥ 12 weeks\n3. Subject is willing and able to comply with the trial testing, procedures, and follow-up schedule\n4. History of a histologically confirmed diagnosis of glioblastoma per 2021 WHO criteria\n5. Have radiographic evidence of tumor progression\u002Frecurrence with measurable disease (≥ 1 cm to ≤ 5cm bidirectional diameters) by contrast-enhancement on MRI, according to RANO criteria\n6. Prior surgery and treatment with combination of radiotherapy and chemotherapy ± Tumor Treating Fields (Optune®)\n7. Prior cranial radiation dose \\\u003C 66 Gy\n8. WHO performance status ≤ 2\n9. The interval since completion of cranial radiotherapy must be \\> 6 months, unless there is tissue confirmation of tumor recurrence\u002Fprogression outside the previous radiation treatment field, in which case the interval since completion of cranial radiation must be at least 12 weeks\n10. Interval since last systemic therapy until presumed date of intervention ≥ 1 cycle or ≥ 2 biological half-lives, i.e.\n\n    1. ≥ 4 weeks since last dose of temozolomide\n    2. ≥ 6 weeks since last dose of lomustine or other nitrosourea\n    3. ≥ 2 weeks since last dose of a small molecule targeted agent (Tyrosine Kinase Inhibitor or similar)\n    4. ≥ 6 weeks from last dose of last intravenous bevacizumab infusion, or other antibody-based VEGF therapy\n11. If receiving steroids, patient should be on a stable or decreasing dose equivalent to dexamethasone ≤ 6 mg\u002Fd, for at least 7 days prior to registration\n12. Have adequate organ and bone marrow function within 14 days prior to registration, as defined below:\n\n    1. INR ≤ 1.2 (in absence of anticoagulation)\n    2. Platelets ≥ 100,000\u002FL\n    3. Creatinine ≤1.5 mg\u002FdL\n    4. Absolute Neutrophil Count ≥1.5 x 10\\^9\u002FL\n    5. Hemoglobin ≥9.0 g\u002FdL\n13. Have a negative pregnancy test within 14 days prior to registration on study (for FOCBP, female of child-bearing potential)\n14. Subject is a male or non-pregnant female. If female of child-bearing potential, and if sexually active must be using, or agree to use, a medically acceptable method of birth control as confirmed by the investigator\n15. Angiographic Mapping Inclusion Criteria:\n\n    1. Accessible neurovascular anatomy that allows for safe microcatheter placement (up to two locations) to infuse TheraSphere GBM to treat all of the T1 enhancing component of target lesion confirmed by neuro-interventional team.\n    2. Total treatment volume is ≤ 150cc as determined by multidisciplinary team.\n16. Additional Inclusion Criteria:\n\n    1. Group A: perfused volume encompasses the non-dominant hemisphere and non-eloquent regions of the brain\n    2. Group B: perfused volume encompasses the non-dominant hemisphere and eloquent regions of the brain\n    3. Group C: perfused volume encompasses the dominant hemisphere and non-eloquent regions of the brain\n    4. Group D: perfused volume encompasses the dominant hemisphere and eloquent regions of the brain\n\nExclusion Criteria:\n\n1. Have bilateral gadolinium enhancing disease, tumor located in the posterior fossa, tumor involving critical subcortical structures (thalamus\u002Fhypothalamus, midbrain, brainstem, corticospinal tract, internal capsule, cerebral peduncle), tumor approximating or invading the brainstem and\u002For optic chiasma, leptomeningeal disease, or extracranial metastatic disease\n2. Have received more than 1 course of prior cranial radiotherapy (EBRT)\n3. Have received radiosurgery, brachytherapy, or hypofractionated radiotherapy\n4. Have received more than 2 systemic treatment protocols (lines of treatment), not including maintenance temozolomide\n5. Have received prior intra-arterial cerebral infusion therapy\n6. Have received more than 2 surgical GBM-related procedures\n7. Have received prior thoracic radiation therapy\n8. Are at increased risk of wound dehiscence by the discretion of the investigators (e.g. brain surgery within the last 3 months, poor skin condition, and\u002For previously infected surgical field or any other condition that is of increased infectious risk in the opinion of the neurosurgeon)\n9. Have uncontrolled epilepsy\n10. Have severe and\u002For insufficiently controlled intercurrent illness; patients with the following are not eligible:\n\n    1. Hypertension grade 3 or higher without adequate control on medications\n    2. Symptomatic or unstable cardiac disease, known to have right-to-left shunts, or severe pulmonary hypertension (pulmonary artery pressure \\> 90 mmHg)\n    3. Pulmonary insufficiency (arterial oxygen pressure (Pa,O2) of \\\u003C 60 mmHg, or oxygen saturation (Sa,O2) of \\\u003C 90%) as measured by fingertip pulse oximeter\n    4. Ongoing or active bacterial or viral infection requiring systemic treatment (including HIV)\n    5. Pneumonitis\n    6. Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n    7. Peripheral Neuropathy ≥ grade 1\n    8. Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety, study endpoints or longevity\n11. Are currently pregnant or breast feeding (unless patient agrees to stop breastfeeding)\n12. Patients with a history of an active other malignancy within 1 year prior to registration. NOTE: Exceptions to this requirement include adequately treated non-melanoma skin cancer or lentigo maligna or carcinoma in situ without evidence of disease, or recurrent glioblastoma\n13. Patients with a history of ischemic cerebral disease and\u002For at risk of cerebral herniation\n14. Medical contraindication to undergo contrast-enhanced magnetic resonance imaging (MRI)\n15. Known history of hypersensitivity reactions to iodinated and\u002For gadolinium-based contrast\n16. Subject has received any other investigational agents within 4 weeks of treatment, or is currently participating, or plans to participate in, another investigational trial that may confound the results of this trial (unless written approval is received from the Boston Scientific study team)\n17. Angiographic Mapping Exclusion Criteria: Patients with significant vascular disease, significant AV shunting, or anatomic tortuosity on MR\u002FCT Angiogram precluding safe or feasible vascular access",{"count":185,"type":22},36,[60],"The FRONTIER Study is a prospective, interventional, single-arm, multi-center, study to assess the safety and technical feasibility of TheraSphere GBM in patients with recurrent GBM.",[189,29],"Glioblastoma Multiforme",{"date":168,"type":40},{"date":192,"type":40},"2022-07-30",{"date":194,"type":22},"2027-04-30",{"name":196,"class":47},"Boston Scientific Corporation",9,{"id":199,"slug":200,"hasResults":12,"nctId":201,"briefTitle":202,"officialTitle":203,"acronym":4,"eligibilityCriteria":204,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":205,"enrollmentInfo":206,"targetDuration":4,"studyType":23,"phases":208,"briefSummary":209,"conditions":210,"keywords":222,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":229,"lastUpdatePostDateStruct":230,"startDateStruct":231,"completionDateStruct":233,"leadSponsor":235,"locationsCount":75},"100624942","phase-1-novel-indenoisoquinolone-cmyctopoisomerase-1-inhibitor-lmp744-in-recurrent-glioblastoma-100624942","NCT07416188","Novel Indenoisoquinolone CMYC\u002FTOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma","Phase 1\u002FPhase 2 Open Label Trial of a Novel Indenoisoquinolone C-MYC\u002FTOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma","* INCLUSION CRITERIA:\n\nParticipant must meet all the following inclusion criteria to be deemed eligible for this study:\n\n* Participants \\>= 18 years of age\n* Tissue-based diagnosis of recurrent glioblastoma, IDH-wildtype by a neuropathologist\n* Karnofsky Performance Status (KPS) \\>60\n* Willing to use effective birth control method\n\n  --The effects of LMP744 on developing human fetuses are unknown. Therefore, females of childbearing potential and their male partners must be willing to use an effective method of contraception during the clinical study (hormonal, barrier, surgical, or abstinence) before study enrollment and for 6 months after the last dose of the study drug. If the female becomes pregnant or suspects she is pregnant while participating in this study, she must inform her treating physician immediately.\n* Agreeable to undergo surgical intervention for brain biopsy and\u002For resection.\n\n  * Initial diagnostic biopsy under 03-N-0164 will be performed to confirm recurrent disease and obtain pre-treatment tissue.\n  * The surgical intervention may include stereotactic\u002Fneedle biopsy, open biopsy, and\u002For resection, as determined by neurosurgical assessment. Only participants for whom gross total resection of tumor is not expected to be achievable will be included in the study.\n* Willing and able to appoint a durable power of attorney\n* Able to provide informed consent or have a legally authorized representative (LAR) to provide consent, if incapacitated.\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Pregnant and\u002For nursing females\n\n  --As LMP744 is a novel agent with the potential for teratogenic or abortifacient effects, pregnant and\u002For nursing females will be excluded from receiving drug\n* Significant medical co-morbidities that would compromise the participant s ability to tolerate LMP744 and which cannot reasonably be controlled (per the investigator s judgment, such as poorly controlled chronic kidney disease and\u002For poorly controlled congestive heart failure)\n* Social situations that would limit compliance with study requirements, such as chronic homelessness\n* Prior chemotherapy or biologic therapy completed within 4 weeks (6 weeks for nitrosoureas and mitomycin C) or a duration of 5 half-lives (whichever is shorter)\n* Additional malignancy diagnosed or requiring active treatment within 1 year of screening\n* Unable to undergo an MRI scan of the brain\n* Active autoimmune disease that requires systemic treatment within 2 years of screening\n* Cardiac disease\n\n  * \\>=2 MIs\n  * \\>=2 coronary revascularization procedures\n  * Cardiac Troponin T or I \\>= 2x the institutional upper limit of normal at screening\n  * Ejection fraction \\\u003C45% on screening echocardiogram\n* Chronic hypokalemia (K\\\u003C2.5 mmol\u002FL)\n* Human Immunodeficiency Virus (HIV)\n\n  * Known history of HIV\n  * Positive HIV 1\u002F2 at screening.\n* Active Hepatitis B or Hepatitis C infection at screening\n* Active infection requiring systemic antibacterial, antiviral or antifungal therapy \\\u003C7 days prior to initiation of study drug\n* Recipient of autologous or allogeneic T cells\n* Solid organ or tissue transplant recipients","99 Years",{"count":207,"type":22},40,[60,163],"Background:\n\nGlioblastoma is a common brain cancer in adults. Treatment includes surgery, radiation, and chemotherapy. But this cancer can return after treatment and is often fatal. Researchers want to know if a study drug (LMP744) can kill glioblastoma tumor cells.\n\nObjective:\n\nTo test LMP744 in people with glioblastoma.\n\nEligibility:\n\nPeople aged 18 years or older with glioblastoma that returned after treatment.\n\nDesign:\n\nParticipants will be screened. They will have a surgery to remove a small sample of tumor tissue (biopsy) from the brain. This will be done under protocol 03-N-0164. They will stay in the clinic for 1 night. They will also have imaging scans and tests of their heart function.\n\nParticipants will have a central line installed: A flexible tube will be inserted into a vein in the chest. It will be attached to a \"port\" under the skin. This port will be used to draw blood and give medicines without having to insert new needles into a vein.\n\nLMP744 will be given through the central line for 5 days in a row. Participants will remain in the clinic for this time.\n\nParticipants will then have a second surgery to remove as much of their tumor as possible. They will remain in the clinic until they recover from the surgery. Then they will recover at home after surgery.\n\nParticipants will return to the clinic to receive the study drug for 5 days in a row through the central line, once a month for up to 12 months. Blood tests, heart function tests, and periodic imaging scans will be repeated during these visits.\n\nParticipants will continue to have telehealth visits every 3 months after they stop taking the drug.",[29,211,212,213,189,214,215,90,216,217,30,218,219,220,221],"Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype","Relapsed Cancer","Recurrent Tumor","Recurring Glioblastoma","Brain and Central Nervous System Tumors","Glioblastomas","Grade IV Astrocytoma","Recurrent Glioma (Glioblastoma Multiforme)","High Grade Glioma","Glioma, Malignant","Brain Cancer",[29,90,223,224,225,226,227,228,221],"Neoplasms","Neoplasms, Nerve Tissue","Neoplasms by Histological Type","Glioblastoma Multiforme (GBM)","Phase I","Phase II","2026-07-29",{"date":166,"type":40},{"date":232,"type":40},"2026-07-15",{"date":234,"type":22},"2032-12-31",{"name":236,"class":104},"National Institute of Neurological Disorders and Stroke (NINDS)",{"id":238,"slug":239,"hasResults":12,"nctId":240,"briefTitle":241,"officialTitle":242,"acronym":243,"eligibilityCriteria":244,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":245,"enrollmentInfo":246,"targetDuration":4,"studyType":23,"phases":248,"briefSummary":249,"conditions":250,"keywords":252,"overallStatus":255,"whyStopped":4,"lastUpdateSubmitDate":256,"lastUpdatePostDateStruct":257,"startDateStruct":258,"completionDateStruct":260,"leadSponsor":262,"locationsCount":152},"100649806","phase-1-olig2-inhibitor-ct-179-for-recurrent-and-newly-diagnosed-glioblastoma-100649806","NCT07739017","OLIG2 Inhibitor CT-179 for Recurrent and Newly-diagnosed Glioblastoma","A Phase 1, Two-Part, Accelerated Dose Titration Trial of CT-179 as Monotherapy in the Treatment of Recurrent Glioblastoma and in Combination With Radiation Therapy in the Treatment of Newly Diagnosed MGMT-Unmethylated Glioblastoma","OPAL","Inclusion Criteria:\n\n* Male or female aged ≥ 18 years at the time of signing informed consent\n* Supratentorial, histologically confirmed diagnosis of primary GBM that meets the current diagnostic classification: 2021 WHO Classification of Tumors of the Central Nervous System\n* KPS score ≥ 70\n* Adequate organ function\n* Contraception during study participation, as applicable\n* Able to swallow tablets\n\nExclusion Criteria:\n\n* Treatment with an investigational agent within the last 30 days excluding 5- aminolevulinic acid (5-ALA)\n* Placement of Gliadel wafers or similar local therapy at time of surgery\n* Receive bevacizumab\n* Evidence of intracranial or intra-tumoral hemorrhage\n* Significant concomitant disorder or serious intercurrent illness\n* History of prior malignancy, except adequately treated non-melanoma skin cancer, carcinoma in-situ of the cervix, or disease-free for more than 5 years\n* Treatment for HIV, hepatitis B, or hepatitis C\n* Any gastrointestinal disorder that could result in reduced absorption of CT-179\n* Any psychiatric illness or social situation that would limit compliance with study requirements\n* Dose of dexamethasone higher than 4 mg\u002Fday within 1 week of the first dose of study medication","75 Years",{"count":247,"type":22},54,[60],"This is a first-in-human Phase 1 two-part, open-label, multi-center, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and maximum tolerated dose (MTD) of CT-179 in patients with recurrent glioblastoma and newly diagnosed MGMT-unmethylated glioblastoma who are eligible to receive radiation therapy following surgery, and to establish the recommended Phase 2 dose.",[29,251],"Newly Diagnosed MGMT Unmethylated Glioblastoma",[28,253,254],"Brain Tumour","OLIG2","NOT_YET_RECRUITING","2026-07-27",{"date":168,"type":40},{"date":259,"type":22},"2026-12",{"date":261,"type":22},"2028-09",{"name":263,"class":74},"Olivia Newton-John Cancer Research Institute",{"id":265,"slug":266,"hasResults":12,"nctId":267,"briefTitle":268,"officialTitle":269,"acronym":4,"eligibilityCriteria":270,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":271,"targetDuration":4,"studyType":23,"phases":273,"briefSummary":274,"conditions":275,"keywords":276,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":256,"lastUpdatePostDateStruct":277,"startDateStruct":278,"completionDateStruct":280,"leadSponsor":282,"locationsCount":75},"100461131","spectroscopic-mri-proton-therapy-and-avastin-for-recurrent-glioblastoma-100461131","NCT05284643","Spectroscopic MRI, Proton Therapy, and Avastin for Recurrent Glioblastoma","Pilot Trial of Spectroscopic MRI-guided, Dose-Escalated Proton Radiation Therapy and Bevacizumab for Recurrent Glioblastoma","Inclusion Criteria:\n\nA. Recurrent glioblastoma (or variants such as gliosarcoma) based on one of the following criteria:\n\n1. An area of MRI enhancement consistent with glioblastoma outside of the initial high dose radiation field.\n2. Biopsy or resection proven recurrent glioblastoma.\n3. Progressive glioblastoma based on advanced imaging (brain positron emission tomography (PET), perfusion MRI, or clinical MR Spectroscopy)\n\nB. Pathology diagnosis of glioblastoma, or variants such as gliosarcoma, on initial and\u002For reresection by 2021 WHO glioblastoma criteria. Prior pathology reports or specimens can be reexamined and reclassified as glioblastoma based on current criteria.\n\nC. Total area of recurrence on T1 post-contrast MRI (including all nodules of likely tumor) have a linear maximum measurement of 6 cm or less.\n\nD. Patients must have received prior brain radiation therapy for glioma in conventional fractionation (1.8 - 2 Gy per fraction, total dose maximum 63 Gy).\n\nE. Patients must have completed prior brain radiation four to six months or more prior to study treatment for recurrent tumors that are at least half based within the high dose (\\> 46 Gy) radiation field.\n\n1. For \"marginal\" or \"out of field\" radiation failures where at least half of the enhancing disease is outside of the prior high dose radiation field but there is field overlap, patients must have completed prior radiation at least four months or more prior to study treatment.\n2. For \"in field\" radiation failures where at least half of the enhancing disease is within the prior high dose radiation field, patients must have completed prior radiation at least six months or more prior to study treatment.\n\nF. A minimum time must be elapsed from the administration of any prior anti-tumor or investigational agents to initiation of study treatments on this protocol as follows:\n\n1. 28 days or 5 half-lives, whichever is shorter, elapsed from the administration of any experimental agent prior to initiation of study treatment.\n2. 28 days elapsed from the administration of any prior cytotoxic agents except\n\ni. 14 days from vincristine and ≥ 21 days from procarbazine and Temozolomide (TMZ) prior to initiation of study treatment.\n\nG. Age at least 18.\n\nH. Patients must be able to have MRI scans.\n\nI. Patient must be able to provide written informed consent.\n\nJ. ECOG performance status 0-2.\n\nK. Life expectancy greater than 12 weeks at the discretion of the enrolling investigator.qa\n\nL. Female subjects should have a negative serum pregnancy test unless they confirm their menopausal status and\u002For have undergone previous hysterectomy and\u002For oophorectomy.\n\nM. Both men and women with childbearing potential should agree to use effective contraception for the duration of the treatment and for at least 6 months after the last treatment since medications that will be used can be harmful for the embryo. See contraception requirements, protocol section 4.16.\n\nN. Complete blood count (CBC)\u002Fdifferential within 21 days prior to registration with absolute neutrophil count at least 1500 cells\u002Fmm2, platelets at least 75,000 cells\u002Fmm2, and hemoglobin at least 9.0 g\u002Fdl (transfusion or other intervention to achieve Hgb of 9.0 or greater is acceptable).\n\nO. Liver function tests must demonstrate total bilirubin 2 mg\u002FdL or less, serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal or less within 21 days prior to registration.\n\nP. Kidney function tests must indicate serum creatinine 1.8 mg\u002FdL or less within 21 days prior to registration and the following:\n\na. Urine protein: creatinine (UPC) ratio \\\u003C 1.0 within 14 days prior to registration OR urine dipstick for proteinuria ≤ 2+ (patients discovered to have \\> 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is \\\u003C1.0 to be eligible. If the UPC ratio is ≥ 1.0 then the patients should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in 24 hours to be eligible).\n\ni. Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formulas:\n\n1. \\[urine protein\\]\u002F\\[urine creatinine\\]: if both protein and creatinine are reported in mg\u002FdL\n2. \\[(urine protein) x0.088\\]\u002F\\[urine creatinine\\]: if urine creatinine is reported in mmol\u002FL\n\nQ. Patients on full-dose anticoagulants must meet both of the following criteria:\n\n1. No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)\n2. In-range international normalized ratio (INR) (typically 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, within 21 days prior to registration\n\nExclusion Criteria:\n\nA. Brain malignancies other than glioblastoma (or variants such as gliosarcoma) by WHO 2021 criteria (benign lesions like meningioma are allowed)\n\nB. Glioma that has not previously undergone standard first line therapies including a first course of radiation therapy.\n\nC. Glioma that has already undergone a second course of radiation therapy.\n\nD. Multi-focal disease (separate enhancing nodules across multiple brain lobes). Note: Multiple nodules in the same region are allowed as long as the total linear diameter is 6 cm or less.\n\nE. Patients who have had treatment with Bevacizumab in the past.\n\nF. Patients who will receive chemotherapy concurrent with study therapy other than bevacizumab.\n\nG. Patients with recurrent Glioblastoma (rGBM) based in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: temporal lobe below the level of the floor of the third ventricle, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum (these regions have known sMRI artifact).\n\nH. Pregnant or breastfeeding patients.\n\nI. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year. Non-invasive tumors are permissible (e.g., carcinoma in situ).\n\nJ. Severe active co-morbidities as follows:\n\n1. Unstable angina and\u002For congestive heart failure requiring hospitalization within the last 6 months prior to registration.\n2. Transmural myocardial infarction within the last 6 months prior to registration.\n3. History of stroke or transient ischemic attack within 6 months prior to registration.\n4. Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.\n5. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.\n6. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.\n7. Hepatic insufficiency resulting in clinical jaundice and\u002For coagulation defects; note, however, that laboratory tests for liver function other than screening panel (Section 3.1) and coagulation parameters are not required for entry into this protocol.\n8. Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.\n\nK. Pregnancy or women of childbearing potential and men who are sexually active and not willing\u002Fable to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.\n\nL. Prior allergic reaction to the study drug (Bevacizumab)\n\nM. Prior history of hypertensive crisis or hypertensive encephalopathy.\n\nN. History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration\n\nO. Gastrointestinal bleeding or any other hemorrhage\u002Fbleeding event Common Terminology Criteria for Adverse Events (CTCAE), v. 4 grade 3 or greater within 30 days prior to registration\n\nP. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration (with the exception of craniotomy)\n\nQ. Concurrent receipt of any other investigational agents",{"count":272,"type":22},96,[139],"The purpose of this research is to find hidden cancer with an experimental magnetic resonance imaging (MRI) scan called spectroscopic magnetic resonance imaging (sMRI). That spectroscopic MRI scan will be used to increase the area of the brain receiving radiation and then the dose of radiation in attempt to kill more of the cancer. Proton radiotherapy and bevacizumab (Avastin) are used to minimize the possible side effects of this approach.",[29],[221],{"date":229,"type":40},{"date":279,"type":40},"2022-09-30",{"date":281,"type":22},"2029-09-30",{"name":283,"class":74},"University of Miami",{"id":285,"slug":286,"hasResults":12,"nctId":287,"briefTitle":288,"officialTitle":289,"acronym":4,"eligibilityCriteria":290,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":291,"enrollmentInfo":292,"targetDuration":4,"studyType":23,"phases":294,"briefSummary":295,"conditions":296,"keywords":298,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":302,"lastUpdatePostDateStruct":303,"startDateStruct":305,"completionDateStruct":307,"leadSponsor":309,"locationsCount":311},"100586048","alpha-radiation-emitters-device-dart-for-the-treatment-of-recurrent-glioblastoma-100586048","NCT06910306","Alpha Radiation Emitters Device (DaRT) for the Treatment of Recurrent Glioblastoma","A Study to Assess the Feasibility and Safety of Intratumoral Diffusing Alpha Emitters for the Treatment of Recurrent Glioblastoma","Inclusion Criteria:\n\n* Males and females ≥ 18 and ≤ 85 years of age\n* Patients must have histologically confirmed diagnosis of WHO grade IV glioblastoma (including variants such as gliosarcoma, giant cell glioblastoma).\n* Single, gadolinium-enhancing tumor recurrence ≤ 3cm in maximum diameter\n* Patient not amenable for surgical resection due to any of the following but not limited reasons: patient refusal, medically ineligible, surgically too high risk due to tumor location in a deep and\u002For eloquent location.\n* Prior history of central nervous system (CNS) radiation (standard dose) with 50.4-60 Gy delivered in 1.8 Gy-2.0 Gy fractions with concurrent temozolomide (if the patient has received a non-standard fractionation or radiation dose, such as 40 Gy in 15 fractions.\n* Patients must have a time interval ≥4 months between completion of prior radiation and trial registration and have tumor progression per RANO criteria\n* Patients must have a measurable disease per RANO criteria\n* Estimated life expectancy is more than 6 months\n* Target lesion amenable for coverage by the DaRT sources\n* Patient must either have had recent subtotal surgery\u002Fbiopsy following tumor recurrence (at least 6 weeks from trial registration) or must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced MRI scan within 21 days prior to trial registration. If surgery was performed, must have a post-operative MRI scan within 21 days prior to trial registration.\n* Patients have recovered from prior therapy side effects and must be at least 4 weeks post administration of chemotherapies or investigational agents with the exception of nitrosureas (such as Carmustine, Fotemustine, Lomustine) which requires 42 days of washout.\n* Karnofsky performance score (KPS) of at least 60 documented within 14 days prior to trial registration\n* Patients must have adequate biological parameters as demonstrated by the following blood counts at initial screening obtained ≤ 14 days prior to starting treatment Absolute neutrophil count (ANC) ≥ 1.5 × 109\u002FL Platelet count ≥ 100,000\u002Fmm3 (80 × 109\u002FL) Hemoglobin (Hgb) ≥ 9 g\u002FdL.\n* Patients must have the following blood chemistry levels at initial screening obtained ≤ 14 days prior to starting treatment AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal range (ULN) Total bilirubin ≤ 1.5 × ULN\n* Effective contraception must be used by both male and female patients while on the study and for up to 3 months following treatment\n* Patient must have been informed about the nature of the study, and must have agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities\n\nExclusion Criteria:\n\n* Medical contraindication to MRI (cardiac devices are allowed if MRI compatible)\n* More than 3 relapses per RANO criteria\n* Acquired and or genetic clinical bleeding tendency\n* Suspicious of infratentorial or leptomeningeal or intraventricular disease\n* Concomitant chemotherapy or any other systemic therapy not allowed in the protocol\n* Recent or current (within 6 weeks) therapy with VEF or a VEGFR inhibitor\n* Immunocompromised state due to either transplant or AIDS\n* Prior allergic reaction to the study drugs\n* History of hypertensive crisis or hypertensive encephalopathy\n* Uncontrolled hypertension (defined as either \\>150 mm\u002FHg for systolic and \\>90mm\u002FHg for diastolic)\n* History of a non-healing wound, ulcer, gastrointestinal bleed (\\> grade 3), traumatic injury, or bone fracture within 90 days prior to registration Volunteers participating in another interventional study in the past 30 days which might conflict with the endpoints of this study or the evaluation of response or toxicity of DaRT\n* High probability of protocol non-compliance (in opinion of investigator)\n* Pregnancy or lactation\n* Collagenous diseases, specifically systemic lupus erythematosus, scleroderma, or dermatomyositis","85 Years",{"count":293,"type":22},10,[139],"A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for the treatment of recurrent Glioblastoma",[29,297],"Recurrent Gliomas",[29,299,30,300,301],"Brachytherapy","Alpha DaRT sources","Intratumoral Diffusing Alpha Emitters","2026-07-19",{"date":304,"type":40},"2026-07-21",{"date":306,"type":40},"2025-10-01",{"date":308,"type":22},"2026-12-01",{"name":310,"class":47},"Alpha Tau Medical LTD.",3,{"id":313,"slug":314,"hasResults":12,"nctId":315,"briefTitle":316,"officialTitle":317,"acronym":318,"eligibilityCriteria":319,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":320,"targetDuration":4,"studyType":23,"phases":322,"briefSummary":324,"conditions":325,"keywords":327,"overallStatus":255,"whyStopped":4,"lastUpdateSubmitDate":335,"lastUpdatePostDateStruct":336,"startDateStruct":338,"completionDateStruct":340,"leadSponsor":342,"locationsCount":75},"100647519","early-phase-1-pilot-radioembolisation-clinical-trial-assessing-safety-and-efficacy-in-recurrent-glioma-100647519","NCT07712770","Pilot Radioembolisation Clinical Trial Assessing Safety and Efficacy in Recurrent Glioma","Pilot Radioembolisation Clinical Trial Assessing Safety and Efficacy in Recurrent Glioma (PRECISE)","PRECISE","Inclusion Criteria:\n\n1. Age ≥18 years at the time of screening\n2. Histomolecular diagnosis of IDH-wildtype glioblastoma (as per WHO 2021)\n3. Prior treatment with radiotherapy and an alkylating agent\n4. Presence of measurable disease on brain MRI, as defined by RANO 2.0 criteria\n5. Radiologically confirmed disease progression as per RANO 2.0 criteria\n6. Lesion confined to a single focus, with a maximum diameter ≤6 cm, and located in a vascular territory amenable to selective intra-arterial catheterisation as assessed on baseline imaging and confirmed by planning angiography, cone beam CT, and \\[99mTc\\]Tc-MAA SPECT\u002FCT (where available)\n7. Stable neurological status; patients with epilepsy may be included if seizures are controlled on a stable dose of anti-epileptic medication\n8. ECOG performance status 0-2\n9. Estimated life expectancy of ≥3 months, in the opinion of the investigator\n10. Adequate haematologic, renal, hepatic, and coagulation function at screening, defined as:\n\n    * Haemoglobin ≥9 g\u002FdL\n    * Absolute neutrophil count ≥1.5 x 109\u002FL\n    * Platelet count ≥100 x 109\u002FL\n    * Serum creatinine ≤1.5 x ULN, or creatinine clearance ≥30 mL\u002Fmin (Cockcroft-Gault formula)\n    * Total bilirubin ≤1.5 x ULN (except patients with known Gilbert's syndrome)\n    * Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2.5 x ULN\n    * International normalized ratio (INR) ≤1.5 x ULN\n    * Prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN\n11. Ability to understand and comply with study requirements and provide written informed consent.\n\nExclusion Criteria:\n\n1. Multifocal glioma recurrence\n2. Tumour located in the posterior fossa or involving\u002Frisking critical subcortical structures (e.g. thalamus, hypothalamus, basal ganglia, internal capsule, cerebral peduncle, midbrain, brainstem, or optic pathways)\n3. Prior treatment with VEGF inhibitors\n4. Prior re-irradiation for progressive or recurrent disease\n5. Any local (surgery or radiotherapy) or systemic anti-cancer therapy within 28 days prior to the planned dose of the investigational treatment\n6. Concurrent use of any anti-cancer therapies, investigational drugs, or biological agents not specified in the protocol\n7. Contraindications to MRI, including but not limited to non-compatible implantable devices or severe claustrophobia\n8. Contraindications to catheter-based angiography, including but not limited to known bleeding disorders, significant vascular abnormalities precluding safe access, and severe allergy to contrast agents\n9. Pregnancy or breastfeeding. Women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception during the study and for at least 4 months after the last procedure.\n10. Any severe or uncontrolled medical condition that, in the investigator's judgement, would pose an unacceptable risk to the patient or interfere with protocol compliance\n11. Cognitive or psychiatric conditions that would limit the ability to provide informed consent or adhere to study procedures\n12. Known hypersensitivity or allergy to 90Y-resin microspheres or any component of the investigational product",{"count":321,"type":22},12,[323],"EARLY_PHASE1","This study is testing a new way of treating brain tumours using tiny radioactive beads called SIR-Spheres® (90Y-labelled Resin Microspheres). These microspheres are placed into the blood vessels that feed the tumour. The treatment gives off radiation inside the tumour to try to stop it from growing.\n\nThis type of treatment is called Selective Internal Radiation Therapy (SIRT), Transarterial Radioembolisation (TARE), or radioembolisation. It is already an accepted treatment for patients with liver cancer. In this study, we are testing if this treatment can be done safely in the brain and how well it works.",[326,29],"Recurrent Glioblastoma IDH Wildtype",[328,329,330,331,332,333,334],"glioblastoma","SIR-spheres","Selective Internal Radiation Therapy","SIRT","Transarterial Radioembolisation","TARE","radioembolisation","2026-07-14",{"date":337,"type":40},"2026-07-17",{"date":339,"type":22},"2026-10",{"date":341,"type":22},"2028-11",{"name":263,"class":74},{"id":344,"slug":345,"hasResults":12,"nctId":346,"briefTitle":347,"officialTitle":348,"acronym":4,"eligibilityCriteria":349,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":350,"targetDuration":4,"studyType":23,"phases":351,"briefSummary":352,"conditions":353,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":335,"lastUpdatePostDateStruct":358,"startDateStruct":359,"completionDateStruct":361,"leadSponsor":363,"locationsCount":75},"100354565","phase-1-msc-dnx-2401-in-treating-patients-with-recurrent-high-grade-glioma-100354565","NCT03896568","MSC-DNX-2401 in Treating Patients With Recurrent High-Grade Glioma","Phase I Clinical Trial of Allogeneic Bone Marrow Human Mesenchymal Stem Cells Loaded With A Tumor Selective Oncolytic Adenovirus, DNX-2401, Administered Via Intra-Arterial Injection in Patients With Recurrent High-Grade Glioma","Inclusion Criteria:\n\nSubjects must meet the following inclusion criteria to be eligible and enroll:\n\n1. Subjects must be willing and able to provide informed consent, undergo and comply with all study assessments, and adhere to the protocol schedule.\n2. Patients with recurrent malignant GBM or gliosarcoma will be eligible. Patients with recurrent anaplastic astrocytoma with wild-type IDH-1 gene will also be eligible if there is a significant enhancing mass on MRI (≥1.0 cm in diameter with upper limit of 5 cm maximal diameter) because their prognosis\u002Fbehavior is similar to GBM. Subjects with an initial diagnosis of an IDH-mutant grade 2 or 3 astrocytoma are also eligible at recurrence if a biopsy at recurrence is determined to be IDH-mutant grade 4 astrocytoma, and there is a significant enhancing mass on MRI (≥1.0 cm in diameter with upper limit of 5 cm maximal diameter). A pathology report constitutes adequate documentation of histology for study inclusion.\n3. Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan after failing prior surgical resection, biopsy, chemotherapy or radiation. A baseline MRI must be performed within 24 days prior to registration. Biopsy is encouraged at the time of recurrence if it is unclear that there is recurrent tumor. However, biopsy is not required if the practicing physician thinks that there is adequate radiographic and clinical evidence for recurrence.\n4. Male or female patients ≥ 18 years of age.\n5. Patients must be able to undergo endovascular treatment based on Doppler studies showing ICA that is less than 50% occluded.\n6. For patients undergoing resection for biological endpoints, tumors must be surgically resectable at the time of baseline evaluation and craniotomy for tumor resection is indicated as part of their standard medical care.\n7. Tumors must be ≥1.0 cm in diameter with upper limit of 5 cm maximal diameter.\n8. Patients must have a Karnofsky performance score ≥ 70.\n9. Patients must have a life expectancy of at least 16 weeks.\n10. Patients must have adequate bone marrow function (absolute granulocyte count \\> 1,500 and platelet count of \\> 75,000), adequate liver function (SGPT and SGOT and bilirubin \\\u003C 2 times institutional normal ranges), and adequate renal function (creatinine \\\u003C 2.0 times institutional normal) prior to starting therapy.\n11. Prothrombin time\u002Finternational normalized ratio (PT\u002FINR) or partial thromboplastin time (PTT) ≤ 1.5x ULN.\n12. Subjects who have received the following chemotherapies must have completed them within the following time periods prior to Baseline\u002FDay 0 of hMSC-DNX2401 delivery with recovery from any drug-related toxic effects to Grade 1, or less, severity:\n\n    * Four weeks from cytotoxic agents (3 weeks from procarbazine or Temozolomide, 2 weeks from vincristine)\n    * 6 weeks from nitrosoureas (CCNU, BCNU)\n    * Four weeks from any targeted investigational agent\n    * One week from non-cytotoxic agents\n13. This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender.\n14. No exclusion to this study will be based on race. Minorities will actively be recruited to participate. The malignant glioma patient population treated at MDACC over the past year is as follows:\n\n    * American Indian or Alaskan Native - 0\n    * Asian or Pacific Islander - \\\u003C2%\n    * Black, not of Hispanic Origin - 3%\n    * Hispanic - 6%\n    * White, not of Hispanic Origin - 88%\n    * Other or Unknown - 2%\n    * Total - 100%\n15. Patients must be 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field (beyond 80% isodose line). However, if a biopsy is undertaken prior to these times and this biopsy documents histological evidence for recurrent disease, then patients will be eligible regardless of the time after radiation.\n16. Patients must be willing to forego other cytotoxic and non-cytotoxic drug or radiation therapy against the tumor while enrolled in the study.\n17. Women of childbearing potential must have a negative urine or serum pregnancy test at screening.\n18. Subjects and their partners must be willing to use effective birth control during the study and for up to 6 months following administration of hMSC-DNX2401. Birth control that is acceptable to use in this study:\n\n    * Using twice the normal protection of birth control (i.e., double-barrier) by using a condom AND spermicidal jelly or foam, or a diaphragm AND spermicidal jelly or foam. A spermicidal jelly or foam must be used in addition to a barrier method (e.g., condom or diaphragm)\n    * Birth control pills (\"The Pill\")\n    * Depot or injectable birth control\n    * IUD (Intrauterine Device)\n    * Birth Control Patch (e.g., Othro Evra®)\n    * NuvaRing®\n    * Surgical sterilization (i.e., tubal ligation or hysterectomy for women or vasectomy for men)\n\nExclusion Criteria:\n\n1. Histology other than GBM, gliosarcoma, IDH wild-type astrocytoma grade III or IDH-mutant astrocytoma grade 4.\n2. Tumor foci detected below the tentorium or beyond the cranial vault.\n3. Tumor within the posterior fossa.\n4. Tumor with leptomeningeal spread.\n5. Difficulty in obtaining vascular access for percutaneous procedure.\n6. Ipsilateral carotid stenosis (\\>50%, by Doppler studies).\n7. Thrombophilias or primary hematological diseases.\n8. Transfusions or medications (G-CSF) to treat pancytopenia or other hematological conditions \\\u003C 28 days prior to Baseline\u002FDay 0\u002FhMSC-DNX2401 administration.\n9. Biologic\u002Fimmunotherapy within 2 weeks of baseline.\n10. Clinical or laboratory evidence of inflammatory and\u002For autoimmune disorders.\n11. Any contraindication for undergoing MRI such as: individuals with pacemakers, epicardial pacer wires, infusion pumps, surgical and\u002For aneurysm clips, shrapnel, metal prosthesis, implants with potential magnetic properties, metallic bodies in the eyes, etc. In addition, subjects must present with tumor that is evaluable by MRI.\n12. Pregnant or nursing females.\n13. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions. All subjects must be afebrile (i.e., \\\u003C38.0° Celsius \\[C\\]).\n14. Any medical condition that precludes surgery or endovascular treatment\n15. Alcoholism (dependency), alcohol or substance abuse within twelve (12) months prior to screening that has caused health consequences.\n16. Immunocompromised subjects or those with autoimmune conditions, active hepatitis (Liver function tests \\> 2x normal) or human immunodeficiency virus (HIV) seropositivity.\n17. Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery. If the medication can be discontinued prior to DNX-2401 injection then the subject may be eligible following consultation with the Study Chair. Low weight heparin and Lovenox (enoxaparin) administered on a temporary limited basis for post procedure DVT prophylaxis is permitted.\n18. History or current diagnosis of any medical or psychological condition that in the Investigator's opinion might interfere with the subject's ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems.\n19. Encephalitis, multiple sclerosis or other central nervous system (CNS) infection or primary CNS disease that would interfere with subject evaluation.\n20. Subjects with known Li-Fraumini Syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways.\n21. Subjects with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, cerebrovascular disease (history of strokes or TIAs in large vessel or small vessel distribution), kidney disease or renal failure, active liver disease, organ transplantation, or significant psychiatric disorder.\n22. Enrollment in a concomitant therapeutic clinical study.\n23. Any condition that prevents compliance with the protocol or adherence to therapy.\n24. For patients enrolled in the biological endpoint phase of the study, patients will be excluded if in the assessment of the surgeon, after resecting the tumor, there is high likelihood of injecting BM-hMSC-DNX2401 into the ventricles.",{"count":185,"type":22},[60],"This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back (recurrent). Oncolytic adenovirus DNX-2401 is made from the common cold virus that has been changed in the laboratory to make it less likely to cause an infection (such as a cold). The virus is also changed to target brain cancer cells and attack them.",[354,355,29,356,357],"IDH1 wt Allele","Recurrent Anaplastic Astrocytoma","Recurrent Gliosarcoma","Recurrent Malignant Glioma",{"date":232,"type":40},{"date":360,"type":40},"2019-02-12",{"date":362,"type":22},"2027-09-30",{"name":364,"class":74},"M.D. Anderson Cancer Center",{"id":366,"slug":367,"hasResults":12,"nctId":368,"briefTitle":369,"officialTitle":370,"acronym":4,"eligibilityCriteria":371,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":372,"targetDuration":4,"studyType":23,"phases":374,"briefSummary":375,"conditions":376,"keywords":378,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":380,"lastUpdatePostDateStruct":381,"startDateStruct":382,"completionDateStruct":384,"leadSponsor":386,"locationsCount":75},"100489995","phase-1-carv3-team-e-t-cells-in-glioblastoma-100489995","NCT05660369","CARv3-TEAM-E T Cells in Glioblastoma","INCIPIENT: INtraventricular CARv3-TEAM-E T Cells for PatIENTs With GBM","Inclusion Criteria:\n\n* Safety Run In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant\n\n  * Participants must have histologically confirmed recurrent GBM or molecular features of GBM with presence of EGFRvIII mutation detected at initial diagnosis. MGMT methylated, unmethylated, or unknown is allowed.\n  * Participants must be at first progression or recurrence and plan is for biopsy or surgical debulking. Participants must have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.\n\nParticipants must be 2 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent before proceeding with collection or treatment. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.\n\n* ARM 2: Newly Diagnosed GBM, EGFRvIII mutant (will only open once safety is confirmed in Arms 1 and 3)\n\n  * Participants must have histologically confirmed newly diagnosed GBM with presence of EGFRvIII mutation and their tumors must be MGMT unmethylated.\n  * Treatment planned with involved field radiation alone without concomitant or sequential temozolomide.\n* ARM 3: Recurrent GBM, EGFRvIII negative\n\n  * Participants must have histologically confirmed recurrent GBM with EGFR amplification but no EGFRvIII mutation based on initial diagnostic tissue.\n  * Participants must be at first recurrence and plan is for biopsy or surgical debulking. Participants must have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.\n\nParticipants must be 2 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.\n\n* ARM 1: Recurrent GBM, EGFRvIII mutant and ARM 3: Recurrent GBM, EGFRvIII negative:\n\n  * Must be at least 3 months from completion of radiation or evidence of progression is outside the high dose radiation field.\n* Safety Run-In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant and ARM 3: Recurrent GBM, EGFRvIII negative:\n\n  * Participants must have measurable disease, defined as at least one lesion ≥10 mm (≥1 cm) with MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.\n* ALL ARMS:\n\n  * Patients cannot have posterior fossa or intramedullary spine-only disease. Leptomeningeal disease is allowed anywhere in the neuroaxis. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.\n  * Resolution of AEs from any prior systemic anticancer therapy or radiotherapy to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy)\n  * Medically able and willing to undergo placement of an Ommaya reservoir.\n  * Steroid dose anticipated to be ≤ 4 mg of dexamethasone a day or equivalent at time of first CAR-v3-TEAM-E infusion.\n  * Age ≥18 years\n  * Karnofsky ≥60%\n  * Must be able to undergo an MRI with contrast.\n  * Life expectancy of greater than 3 months.\n  * Participants must have adequate organ and marrow function as defined below:\n\n    * Absolute neutrophil count ≥1,000\u002FmcL\n    * Platelets ≥80,000\u002FmcL\n    * Total bilirubin ≤ institutional upper limit of normal (ULN); For patients with Gilbert's syndrome, total bilirubin can be ≤ 3xULN.\n    * AST(SGOT)\u002FALT(SGPT) ≤3 × institutional ULN\n    * CrCl ≥ 60 mL\u002Fmin\n  * Participant has no prior history of malignancy, unless the subject has been free of the disease for ≥5 years with the exception of the following noninvasive malignancies:\n\n    * Basal cell carcinoma of the skin\n    * Squamous cell carcinoma of the skin\n    * Carcinoma in situ of the cervix\n    * Carcinoma in situ of the breast\n    * Incidental histologic finding of prostate cancer (T1a or T1b) or prostate cancer that is curative\n  * Left ventricular ejection fraction \\>50% as determined by TTE.\n  * The effects of CARv3-TEAM-E on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CARv3-TEAM-E administration.\n  * Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Intraparenchymal posterior fossa disease\n* Intramedullary spinal disease as the only site of disease.\n* Prior EGFRvIII targeted therapies.\n* Prior bevacizumab treatment.\n* Treatment with an any prior gene-therapy or gene-modified cellular therapy.\n* Patients with a VP shunt or patients needing a shunt in the immediate future are excluded from participating\n* Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids above physiologic dosing). Intermittent topical, inhaled, or intranasal corticosteroids are allowed\n* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> Grade 1) with the exception of alopecia.\n* Participants who are receiving any other investigational agents.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CARv3-TEAM-E (ex. cetuximab).\n* Participants with uncontrolled intercurrent illness.\n* Human immunodeficiency virus (HIV)-infected participants are not eligible.\n* Participants with evidence of chronic hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection are not eligible.\n* Participants with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CARv3-TEAM-E , breastfeeding should be discontinued if the mother is treated with CARv3-TEAM-E.\n* For Arm 2, prior to CARv3-TEAM-E Infusion, the following criteria should be confirmed in addition to the relevant criteria above:\n\n  * Participants must have completed 75% of the planned 6 weeks of involved field radiation without temozolomide\n  * Tumor location and size criteria as in 3.1.7 above.\n  * Prior cancer directed therapy other than radiation is not allowed.",{"count":373,"type":22},21,[60],"The goal of this research study is to determine the best dose of CARv3-TEAM-E T Cells for treating participants with glioblastoma.\n\nThe name of the treatment intervention used in this research study is:\n\n-CARv3-TEAM-E T Cells (or Autologous T lymphocytes).",[28,377,29,142],"Malignant Glioma",[28,377,29,142,120,379],"Gene-Transfer Therapy","2026-07-13",{"date":335,"type":40},{"date":383,"type":40},"2023-03-22",{"date":385,"type":22},"2027-09-01",{"name":387,"class":74},"Marcela V. Maus, M.D.,Ph.D.",{"id":389,"slug":390,"hasResults":12,"nctId":391,"briefTitle":392,"officialTitle":393,"acronym":4,"eligibilityCriteria":394,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":395,"targetDuration":4,"studyType":23,"phases":397,"briefSummary":398,"conditions":399,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":402,"lastUpdatePostDateStruct":403,"startDateStruct":405,"completionDateStruct":407,"leadSponsor":409,"locationsCount":75},"100578725","phase-1-intracranial-genetically-modified-immune-cells-tgfr2koil13r2-car-t-cells-for-the-treatment-of-recurrent-or-progressive-glioblastoma-or-grade-3-or-4-idh-mutant-astrocytoma-100578725","NCT06815029","Intracranial Genetically Modified Immune Cells (TGFβR2KO\u002FIL13Rα2 CAR T-Cells) for the Treatment of Recurrent or Progressive Glioblastoma or Grade 3 or 4 IDH-Mutant Astrocytoma","A Phase 1 Trial to Evaluate the Safety of IL13Rα2-Targeting Chimeric Antigen Receptor (CAR) T Cells With CRISPR Knockout of TGFβR2 in Patients With Recurrent or Progressive High-Grade Glioma (HGG)","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n\n  * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter\u002Ftranslator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with surgery\u002FRickham placement and CAR T cell infusion only after the translated main consent form is signed\n* Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval\n* Age: ≥ 18 years\n* Karnofsky performance status (KPS) ≥ 70%, Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Life expectancy ≥ 4 weeks\n* If the participant has a shunt, they must be informed of the following:\n\n  * If the shunt is not programmable, the participant must be willing to have a programmable shunt placed prior to CAR T cell infusion, and\n  * If the shunt is programmable, in order to proceed to the treatment portion of the study, the participant must be able to tolerate their shunt being functionally closed for at least 2 hours\n* Participant has a prior histologically-confirmed diagnosis of a grade 3 or 4 IDH-mutant astrocytoma or glioblastoma, or has a prior histologically-confirmed diagnosis of a grade 2 or 3 astrocytoma and now has radiographic progression consistent with grade 3 or 4 IDH-mutant astrocytoma\n* Relapsed disease: radiographic evidence of recurrence\u002Fprogression of measurable disease after standard therapy, and ≥ 12 weeks after completion of front-line radiation therapy\n* COH clinical pathology confirms IL13Rα2+ tumor expression by immunohistochemistry (H-score ≥ 80)\n* No known contraindications to leukapheresis, steroids, or tocilizumab\n* White blood cell (WBC) \\> 2000 \u002Fdl (or absolute neutrophil count \\[ANC\\] ≥ 1,000\u002Fmm\\^3) (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Platelets ≥ 75,000\u002Fmm\\^3 (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Hemoglobin ≥ 8g\u002Fdl (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Aspartate aminotransferase (AST) ≤ 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Alanine aminotransferase (ALT) ≤ 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Serum creatinine ≤ 1.6 mg\u002FdL (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Oxygen (O2) saturation ≥ 95% on room air (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Seronegative for HIV antigen\u002Fantibody (Ag\u002FAb) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n* Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (to be performed within 14 days prior to leukapheresis unless otherwise stated)\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n\nExclusion Criteria:\n\n* Owing to higher frequency of wound-related complications, participants who require active bevacizumab therapy at the time of enrollment are excluded\n* Participant has not yet recovered from toxicities of prior therapy\n* Uncontrolled seizure activity and\u002For clinically evident progressive encephalopathy\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent\n* Clinically significant uncontrolled illness\n* Active autoimmune disease requiring systemic immunosuppressive therapy\n* Active infection requiring intravenous (IV) antibiotics (e.g., minor scalp infection is not an exclusion)\n* Known history of human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection\n* Other active malignancy. Note: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Females only: Pregnant or breastfeeding\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":396,"type":22},27,[60],"This phase I trial tests the safety, side effects and best dose of TGFβR2KO\u002FIL13Rα2 chimeric antigen receptor (CAR) T-cells given within the skull (intracranial) in treating patients with glioblastoma or IDH-mutant grade 3 or 4 astrocytoma that has come back after a period of improvement (recurrent) or that is growing, spreading, or getting worse (progressive). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. When the cells are taken from the patient's own blood, it is known as autologous. Then the gene for special receptors that bind to a certain proteins on the patient's tumor cells are added to the T cells in the laboratory. The special receptors are called CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain tumors. Giving TGFβR2KO\u002FIL13Rα2 CAR T cells may be safe, tolerable, and\u002For effective in treating patients with recurrent or progressive glioblastoma or grade 3 or 4 IDH-mutant astrocytoma.",[400,401,29],"Recurrent Astrocytoma, IDH-Mutant, Grade 3","Recurrent Astrocytoma, IDH-Mutant, Grade 4","2026-06-25",{"date":404,"type":40},"2026-06-29",{"date":406,"type":40},"2025-06-17",{"date":408,"type":22},"2030-10-11",{"name":410,"class":74},"City of Hope Medical Center",{"id":412,"slug":413,"hasResults":12,"nctId":414,"briefTitle":415,"officialTitle":416,"acronym":4,"eligibilityCriteria":417,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":418,"targetDuration":4,"studyType":23,"phases":420,"briefSummary":421,"conditions":422,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":424,"lastUpdatePostDateStruct":425,"startDateStruct":427,"completionDateStruct":429,"leadSponsor":431,"locationsCount":75},"100634599","phase-1-sitagliptin-in-recurrentprogressive-grade-4-glioma-100634599","NCT07541781","Sitagliptin in Recurrent\u002FProgressive Grade 4 Glioma","Targeting Myeloid-Derived Suppressor Cells in Patients With Recurrent\u002FProgressive Grade 4 Glioma: Phase 1 Trial of Sitagliptin","Inclusion Criteria:\n\nPhase 1b\n\n* Subjects must have histologically or cytologically confirmed WHO grade 4 glioma for which disease recurrence\u002Fprogression after first line therapy is diagnosed by the treating physician.\n* Subjects must not have received sitagliptin or bevacizumab for this disease.\n* Age \\>18 years\n* Performance status: ECOG performance status 0-2\n* Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below:\n\n  1. Hemoglobin ≥ 9 g\u002Fdl\n  2. Absolute neutrophil count ≥ 1,500\u002FmcL\n  3. Platelet count ≥ 100,000\u002FmcL\n  4. Total bilirubin \\\u003C 1.5 x institutional upper limit of normal (ULN)\n  5. AST (SGOT) ≤ 3 X institutional ULN\n  6. ALT (SGPT) ≤ 3 X institutional ULN\n  7. Calculated creatinine clearance \\> 50 mL\u002Fmin\n  8. Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio.\n\n     For UPC ratio \\> 0.5, 24-hour urine protein must be obtained and must be \\\u003C 1000 mg.\n  9. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:\n\n     * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)\n     * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin\n* Subjects must have the ability to understand and the willingness to sign a written informed consent document.\n* Women of childbearing potential, defined as any female who has experienced menarche and has not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy) and is not postmenopausal (≥12 months of spontaneous amenorrhea without an alternative medical cause), must have a negative pregnancy test within 7 days prior to treatment start. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.\n* Subjects must be able to swallow whole tablets.\n* Participants must have controlled blood pressure, defined as systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 100 mg Hg, with or without antihypertensive therapy\n* Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior study treatment\n* Subjects must have the following minimum intervals from prior treatments until planned treatment initiation of Cycle 1 Day 1:\n\n  * surgery - 4 weeks\n  * nitrosoureas - 6 weeks\n  * cytotoxic chemotherapy - standard intervals depending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days after most recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recent dose; etoposide 14 of 21 days, 7 days after last dose.\n  * For drugs not listed, the research nurse, treating investigator, and principal investigator will determine the appropriate interval.\n  * Investigational therapy or non-cytotoxic GBM related therapy - 2 weeks\n* Subject is not deemed as a surgical candidate.\n\nPilot Phase\n\n* Subjects must have histologically or cytologically confirmed WHO grade 4 glioma for which disease recurrence\u002Fprogression after first line therapy is diagnosed by the treating physician.\n* Subjects must not have received sitagliptin or bevacizumab for this disease.\n* Age \\>18 years\n* Performance status: ECOG performance status 0-2\n* Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below:\n\n  1. Hemoglobin ≥ 9 g\u002Fdl\n  2. Absolute neutrophil count ≥ 1,500\u002FmcL\n  3. Platelet count ≥ 100,000\u002FmcL\n  4. Total bilirubin \\\u003C 1.5 x institutional upper limit of normal (ULN)\n  5. AST (SGOT) ≤ 3 X institutional ULN Version date: 30March2026 Page 16\n  6. ALT (SGPT) ≤ 3 X institutional ULN\n  7. Calculated creatinine clearance \\> 50 mL\u002Fmin\n  8. Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio.\n\n     For UPC ratio \\> 0.5, 24-hour urine protein must be obtained and must be \\\u003C 1000 mg.\n  9. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:\n\n     * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)\n     * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin\n* Subjects must have the ability to understand and the willingness to sign a written informed consent document.\n* Women of childbearing potential, defined as any female who has experienced menarche and has not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy) and is not postmenopausal (≥12 months of spontaneous amenorrhea without an alternative medical cause), must have a negative pregnancy test within 7 days of treatment start. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.\n* Subjects must be able to swallow whole tablets.\n* Subjects must have controlled blood pressure, defined as systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 100 mg Hg, with or without antihypertensive therapy\n* Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to treatment start\n* Subjects must have the following minimum intervals from prior treatments until planned treatment initiation of Cycle 1Day1:\n\n  * surgery - 4 weeks\n  * nitrosoureas - 6 weeks\n  * cytotoxic chemotherapy - standard intervals depending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days after most recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recent dose; etoposide 14 of 21 days, 7 days after last dose.\n  * For drugs not listed, the research nurse, treating investigator, and principal investigator will determine the appropriate interval.\n  * Investigational therapy or GBM related non-cytotoxic therapy - 2 weeks\n  * For bevacizumab (if for a different cancer) - 4 weeks from the expected date of protocol surgery\n* Subject is deemed as a surgical candidate.\n\nExclusion Criteria (for phase 1b and pilot phase)\n\n* Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except for alopecia and neuropathy.\n* Subjects receiving any other investigational agents.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to sitagliptin or bevacizumab.\n* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Known HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sitagliptin and\u002For bevacizumab. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy.\n* Other malignancy within the past 2 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or vulva; c) prostate cancer of Gleason Score 6 or less with stable prostate specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas.\n* Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \\[NCI\\] Common Terminology Criteria for Adverse Events Version 5.0 \\[CTCAE v.5.0\\] diarrhea of any etiology at screening).\n* Known active infection with hepatitis B or hepatitis C virus.\n* Pregnant or breastfeeding.\n* Subjects who receive insulin or sulfonylurea for diabetes mellitus.\n* Subjects with history of type 1 diabetes, uncontrolled type 2 diabetes, hypoglycemia requiring medical intervention, or those who are deemed not suitable to receive sitagliptin at the discretion of the investigators.\n* Unable or unwilling to swallow tablets.\n* Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness\u002Fsocial situations that would, in the Investigator's judgment, make the patient inappropriate for this study.\n* Arterial ischemic event (e.g., unstable angina, myocardial infarction, stroke) within 6 months of study consent.\n* Subjects with history of hematologic bleeding disorder.",{"count":419,"type":22},45,[60],"Sitagliptin, when combined with standard-of-care drug bevacizumab, is being tested to 1) find out if it is effective at treating gliomas that have returned or progressed after treatment, and 2) find out what the highest dose of sitagliptin is appropriate to give when combined with bevacizumab.",[90,28,142,29,423],"Grade 4 Malignant Glioma of Brain (Disorder)","2026-06-15",{"date":426,"type":40},"2026-06-17",{"date":428,"type":40},"2026-06-11",{"date":430,"type":22},"2030-06-11",{"name":432,"class":74},"Kailin Yang, MD, PhD",{"id":434,"slug":435,"hasResults":12,"nctId":436,"briefTitle":437,"officialTitle":438,"acronym":4,"eligibilityCriteria":439,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":440,"enrollmentInfo":441,"targetDuration":4,"studyType":23,"phases":443,"briefSummary":444,"conditions":445,"keywords":448,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":455,"lastUpdatePostDateStruct":456,"startDateStruct":458,"completionDateStruct":460,"leadSponsor":462,"locationsCount":152},"100642374","early-phase-1-dosimetry-safety-and-efficacy-study-of-177lulu-xt771-in-patients-with-recurrent-glioblastoma-100642374","NCT07648823","Dosimetry, Safety, and Efficacy Study of [177Lu]Lu-XT771 in Patients With Recurrent Glioblastoma","An Investigator-Initiated Trial to Evaluate the Dosimetry, Safety, Tolerability, and Preliminary Efficacy of a Single-Dose [177Lu]Lu-XT771 Injection in Patients With Recurrent Glioblastoma","Inclusion Criteria:\n\n1. Subject has fully understood the study and voluntarily signed the informed consent form.\n2. Age ≥ 18 and ≤ 80 years old.\n3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.\n4. Life expectancy of at least 3 months.\n5. Histologically confirmed glioblastoma (based on the 2021 WHO Classification of Tumors of the Central Nervous System, 5th edition), and confirmed CA IX\u002FCA XII positive by histology or \\[68Ga\\]Ga-XT771 PET\u002FCT.\n6. Histologically confirmed recurrence of glioblastoma following prior treatments.\n7. Suitable for Ommaya reservoir placement and meets the conditions for drug administration, as judged by the investigator.\n8. Tumor resection cavity volume between 2.5 and 25 cm\\^3.\n9. On a stable or decreasing dose of corticosteroids (≤5 mg\u002Fday of dexamethasone or equivalent) for at least 1 week prior to the first dose.\n10. Toxicity from prior anti-tumor treatments (e.g., chemotherapy, radiotherapy, immunotherapy) recovered to ≤ Grade 1 (excluding alopecia).\n11. Adequate organ and bone marrow function meeting the following criteria:\n\n    * Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 ×10\\^9\u002FL and white blood cell (WBC) count ≥ 3 ×10\\^9 \u002FL (without growth factor support within 28 days prior to dosing); Platelet count ≥ 75 ×10\\^9\u002FL; Hemoglobin ≥ 90 g\u002FL.\n    * Hepatic function: Total bilirubin ≤ 1.5 × ULN (≤ 2.0 × ULN for subjects with liver metastases; ≤ 3.0 × ULN for subjects with confirmed Gilbert's syndrome); ALT and AST ≤ 3 × ULN (\\\u003C 5 × ULN for subjects with liver metastases); Albumin \\> 30 g\u002FL.\n    * Renal function: Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 mL\u002Fmin.\n    * Coagulation: INR ≤ 2.0, APTT ≤ 1.5 × ULN. (Exception: subjects receiving warfarin may have an INR between 2 and 3 inclusive).\n12. Fertile subjects (and their partners) must agree to use highly effective contraceptive methods (e.g., condoms, oral or injectable contraceptives) during the treatment period and for 6 months after the last dose of the study drug.\n\nExclusion Criteria:\n\n1. Received anti-tumor treatments (including radiotherapy, chemotherapy, biological therapy, endocrine therapy, targeted therapy, etc.) within 4 weeks prior to dosing. Exceptions: (1) immunotherapy, nitrosoureas, or mitomycin C within 6 weeks prior to dosing; (2) oral fluorouracils and small molecule targeted drugs within 2 weeks or 5 half-lives (whichever is longer) prior to dosing; (3) Traditional Chinese Medicine with anti-tumor indication within 2 weeks prior to dosing; (4) cranial radiotherapy within 3 months prior to dosing.\n2. Received any other unapproved investigational drug within 4 weeks prior to dosing.\n3. Underwent major organ surgery (excluding needle biopsy) or experienced significant trauma within 4 weeks prior to dosing, or expected to require elective surgery during the study period.\n4. Known or suspected allergy to the study drug or its analogue components.\n5. Inability to undergo contrast-enhanced MRI scans (e.g., due to pacemakers, contrast agent allergy).\n6. Presence of active or uncontrolled infections requiring systemic intravenous treatment, or unexplained fever \\>38.5°C during the screening period or before dosing.\n7. Presence of severe coagulation disorders or evidence of significant bleeding risk; history of gastrointestinal bleeding; any Grade ≥2 bleeding event (CTCAE v5.0) within the past 6 months.\n8. Active Hepatitis B (HBsAg positive and HBV-DNA \\> 500 IU\u002FmL or above the lower limit of detection of the study center) or Active Hepatitis C (HCV antibody positive and HCV-RNA \\> the lower limit of detection of the study center).\n9. Uncontrolled hypertension as judged by the investigator (systolic blood pressure ≥ 160 mmHg and\u002For diastolic blood pressure ≥ 100 mmHg despite standard treatment).\n10. History of severe cardiovascular disease, such as ventricular arrhythmias requiring clinical intervention; QTc interval \\> 480 ms; acute coronary syndrome, congestive heart failure, stroke, or other ≥ Grade III cardiovascular events within 6 months prior to dosing; NYHA class II-IV or LVEF \\\u003C 50%.\n11. History of other uncured malignancies within the past 3 years or concurrently, except for curable in situ cancers (e.g., carcinoma in situ of the cervix, basal cell carcinoma of the skin).\n12. Presence of two or more intracranial lesions, extracranial metastases, or tumors located in the infratentorial compartment or basal ganglia.\n13. Brain MRI indicating that the enhancing edge of the tumor invades the ventricular wall, or the surgical cavity communicates with the ventricle.\n14. Psychiatric disorders or poor compliance.\n15. Pregnant or lactating women.\n16. The investigator considers the subject unsuitable for participation in this clinical study due to other severe systemic diseases or other reasons.","80 Years",{"count":442,"type":22},5,[323],"The primary objective of this study is to evaluate the dosimetry, safety, and tolerability of the investigational radiopharmaceutical \\[177Lu\\]Lu-XT771 in patients with recurrent glioblastoma, an aggressive form of brain cancer. \\[177Lu\\]Lu-XT771 is designed to specifically target and deliver beta radiation directly to tumor cells that overexpress carbonic anhydrase IX and XII (CA IX and CA XII).\n\nThis early-phase, investigator-initiated trial will enroll a small group of approximately 3-5 patients, each receiving a single dose of \\[177Lu\\]Lu-XT771. The drug will be administered locoregionally via an implanted Ommaya reservoir, directly into the tumor cavity. Following administration, patients will be closely monitored using single-photon emission computed tomography\u002Fcomputed tomography (SPECT\u002FCT) to assess the biodistribution of the drug and to quantify the absorbed radiation dose to both the tumor and normal organs.\n\nThe study will also document all adverse events to characterize the safety profile of the treatment and will provide a preliminary assessment of its anti-tumor activity, as measured by progression-free survival. The information gathered from this exploratory study will be used to determine the recommended safe starting dose for future Phase I clinical trials.",[446,29,447,326],"Recurrent Glioblastoma (WHO-Grade IV Glioma)","Glioblastoma (GBM)",[29,449,450,451,452,453,454],"[177Lu]Lu-XT771","Carbonic Anhydrase IX","Carbonic Anhydrase XII","Safety and Tolerability","Dosimetry","Efficacy","2026-06-13",{"date":457,"type":40},"2026-06-16",{"date":459,"type":22},"2026-06-20",{"date":461,"type":22},"2028-06-01",{"name":463,"class":74},"Beijing Tiantan Hospital",{"id":465,"slug":466,"hasResults":12,"nctId":467,"briefTitle":468,"officialTitle":469,"acronym":470,"eligibilityCriteria":471,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":472,"enrollmentInfo":473,"targetDuration":4,"studyType":23,"phases":475,"briefSummary":476,"conditions":477,"keywords":479,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":428,"lastUpdatePostDateStruct":485,"startDateStruct":487,"completionDateStruct":489,"leadSponsor":491,"locationsCount":152},"100619555","phase-1-study-of-an-aav-mediated-dual-payload-gene-therapy-in-patients-with-high-grade-glioma-100619555","NCT07346144","Study of an AAV Mediated Dual-Payload Gene Therapy in Patients With High Grade Glioma","A Phase I\u002FII Study of an AAV-1 Mediated Dual-Payload Gene Therapy in Patients With High Grade Glioma","ADePT","Inclusion Criteria:\n\n* Aged 18-70 years\n* Karnofsky performance status ≥70\n* Newly diagnosed patients: Unifocal, unilateral high-grade glioma based on MRI\n* Recurrent patients: First radiological progression (as determined by the multidisciplinary team \\[MDT\\]) of GBM previously treated with standard care surgery and chemoradiotherapy. Patients must have a prior confirmed histological\u002Fmolecular diagnosis of GBM\n* Newly diagnosed patient: suitable for six weeks of chemoradiotherapy followed by six months of adjuvant temozolomide (Stupp protocol)\n* Debulking surgery is indicated for optimal patient care\n* Able to swallow oral medication\n* Willing to avoid live vaccines\n* Adequate organ function\n* Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to Day 0.\n* All patients must agree to practice true abstinence or to use highly effective contraception\n* Patient is willing and able to give informed consent for participation in the study\n\nExclusion Criteria:\n\n* Patient who is pregnant, lactating or planning pregnancy during the course of the study\n* Immunodeficiency or active auto-immune disease requiring systemic therapy.\n* Active viral, bacterial or fungal infection requiring concurrent antivirals or antibiotics within 7 days of surgery\n* Live vaccine within 28 days prior to Day 0\n* Use of immunosuppressant or immune modulatory medicines within 28 days prior to Day 0\n* History of tuberculosis infection or chest x-ray or computed tomography (CT) chest showing radiological evidence of previous tuberculosis infection\n* Received previous treatment with a gene therapy\n* Significant history of a central nervous system disorder that, in the opinion of the Investigator, would preclude enrolment\n* Major surgery within 28 days prior to Day 0. A stereotactic biopsy is permitted\n* Known hypersensitivity or contraindications to valaciclovir, gadolinium, or any excipients for TGX-007\n* Contraindication to MRI with gadolinium\n* Any condition expected to interfere with the intended timing of debulking surgery\n* Previous non-glioma cancer within 3 years (other than treated squamous\u002Fbasal cell skin cancer, treated early-stage cervical cancer or treated\u002Fbiochemically stable, organ confined prostate cancer)\n* Any other significant disease or disorder which, in the opinion of the Investigator, may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study\n* Patients who have participated in another research study involving an investigational product in the past 12 weeks or 5 half-lives of the product\n* Any psychological, familial, sociological, or geographical consideration potentially hampering compliance with the study protocol and follow up schedule; these conditions should be discussed with the patient before registration in the study\n* Unwilling to allow their general practitioner, if appropriate, to be notified of participation in the study\n\nNewly diagnosed patients only:\n\n* Any prior therapy for glioma\n* Intended use of tumour treating fields\n\nRecurrent patients only:\n\n* Prior toxicities from anti-cancer agents or radiotherapy which have not recovered to ≤Grade 1 severity\n* Intended use of tumour treating fields","70 Years",{"count":474,"type":22},68,[60,163],"The goal of this clinical trial is to first define the Safety and Optimal Biological Dose (OBD) of study drug TGX-007 and to then further investigate the safety and efficacy in patients with newly diagnosed or recurrent Glioblastoma.\n\nTGX-007 is a gene therapy drug delivered by a harmless adeno-associated virus (AAV) vector which delivers two combined therapeutic payloads to enable killing of proliferative cells and activation of an anti-tumour immune response. One is herpes simplex virus thymidine kinase (HSV-tk), which converts the pro-drug valaciclovir into an active drug that can kill tumour cells and the other is interleukin 12 (IL-12), which activates the body's immune system to recognise and fight the tumour.\n\nPatients newly diagnosed with glioblastoma suitable for standard of care surgery and chemoradiotherapy or patients with recurrent glioblastoma suitable for further surgery may be eligible for the study. Patients will receive TGX-007 by a direct intratumoural injection and will then take the pro-drug valacyclovir orally for up to 21 days before proceeding to standard of care surgery.\n\nThe study is split into two phases. Phase I will treat patients at different dose levels of TGX-007 to identify the Optimal Biological Dose that will be used to further expand the study into Phase II. Phase II will expand the number of patients treated at the selected OBD to investigate how effective TGX-007 is at treating newly diagnosed and recurrent GBM.\n\nApproximately 68 people aged 18-70 will take part in the study.",[447,478,29,63],"High Grade Gliomas",[28,120,480,481,482,483,484],"Gene Therapy","AAV","HSV-tk","IL-12","TGX-007",{"date":486,"type":40},"2026-06-12",{"date":488,"type":40},"2026-04-21",{"date":490,"type":22},"2033-09",{"name":492,"class":47},"Trogenix ltd",{"id":494,"slug":495,"hasResults":12,"nctId":496,"briefTitle":497,"officialTitle":498,"acronym":4,"eligibilityCriteria":499,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":440,"enrollmentInfo":500,"targetDuration":4,"studyType":23,"phases":502,"briefSummary":503,"conditions":504,"keywords":505,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":510,"lastUpdatePostDateStruct":511,"startDateStruct":513,"completionDateStruct":515,"leadSponsor":517,"locationsCount":75},"100546027","phase-1-rna-lipid-particle-rna-lp-vaccines-for-recurrent-adult-glioblastoma-gbm-100546027","NCT06389591","RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult Glioblastoma (GBM)","A Phase I Study of RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult Glioblastoma (GBM)","Inclusion Criteria:\n\n* Age \\>\u002F= 18years\n* Histopathologically proven GBM using the 2021 WHO Classification of Tumors of the CNS (WHO CNS5).\n* Unequivocal evidence of tumor progression as documented by brain MRI scan per RANO criteria.\n* Tumor must have a primary supratentorial component at the time of disease progression.\n* Patients must have received surgery and completed Fractionated Radiation therapy as frontline treatment for primary disease, either alone or with concurrent therapy (including temozolomide or another systemic chemotherapy agent). Patients must be at least 12 weeks post chemoradiation completion.\n* Patient must be at least 90 days from completion of prior radiation\n* Any adverse events patient has experienced from prior therapy must have resolved to ≤ Gr. 1 according to CTCAE (NCI Common Terminology Criteria for Adverse Events) v5.0 prior to enrollment\n* Patient must be either weaned off steroids or weaned onto physiologic dosing at the time of enrollment.\n* Patient must be a candidate for surgery\u002Fbiopsy as acceptable standard of care for sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs).\n* A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment.\n* Performance Score: (KPS) ≥ 60. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n* Bone Marrow:\n\n  * ANC (Absolute neutrophil count) ≥ 1,500µl (unsupported)\n  * Platelets ≥ 100\u002Fµl (unsupported for at least 3 days)\n  * Hemoglobin \\> 8 g\u002FdL\n* Renal:\n\n  * BUN ≤ 25 mg\u002Fdl\n  * Creatinine ≤ 1.7 mg\u002Fdl\n* Hepatic\n\n  * Bilirubin ≤ 2.0 mg\u002Fdl\n  * ALT ≤ 5 times institutional upper limits of normal for age\n  * AST ≤ 5 times institutional upper limits of normal for age\n* Patient must be able to give consent.\n* For women of childbearing potential (WOCBP), negative serum\u002Furine pregnancy test at enrollment.\n* WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.\n* Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.\n\nExclusion Criteria:\n\n* Patients who received prior treatment with bevacizumab.\n* Known active infection (requiring treatment by antiviral or antibiotics) or immunosuppressive disease.\n* Patients with multifocal recurrent disease characterized by more than one enhancing lesion separated by noncontiguous T2\u002FFLAIR signal abnormality. Patients with recurrence outside of the original tumor site are eligible if there is stability at the original site of disease.\n* Patients with uncontrolled seizure disorders\n* Any patients that have received any live vaccines within 30 days prior to enrollment\n* Tumors with primary localization to the brainstem or spinal cord\n* Severe, active co-morbidity, defined as follows:\n\n  * Unstable angina and\u002For congestive heart failure requiring hospitalization.\n  * Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months.\n  * Acute bacterial or fungal infection requiring intravenous treatment at study treatment.\n  * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at study treatment\n  * Hepatic insufficiency resulting in clinical jaundice and\u002For coagulation defects.\n  * Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.\n  * Patients with autoimmune disease requiring medical management with immunosuppressants.\n  * Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.\n  * Pregnancy or women of childbearing potential and men who are sexually active and who are unwilling or unable to use an acceptable method of contraception for the entire study period; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.\n* Women of childbearing potential must not be pregnant or breast-feeding.\n* Participants who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to projected first dose of study treatment.\n* Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations",{"count":501,"type":22},24,[60],"This is a Phase I study to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in adult patients with recurrent glioblastoma.",[29],[506,507,508,509],"brain tumor","malignant brain tumor","immunotherapy","adult","2026-05-14",{"date":512,"type":40},"2026-05-15",{"date":514,"type":40},"2024-12-02",{"date":516,"type":22},"2027-12-01",{"name":518,"class":74},"University of Florida",{"id":520,"slug":521,"hasResults":12,"nctId":522,"briefTitle":523,"officialTitle":523,"acronym":4,"eligibilityCriteria":524,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":525,"targetDuration":4,"studyType":23,"phases":526,"briefSummary":527,"conditions":528,"keywords":4,"overallStatus":255,"whyStopped":4,"lastUpdateSubmitDate":534,"lastUpdatePostDateStruct":535,"startDateStruct":537,"completionDateStruct":539,"leadSponsor":541,"locationsCount":75},"100637386","phase-1-a-phase1-clinical-trial-evaluating-locoregional-delivery-of-engineered-nk-cells-containing-il13ra-and-egfviii-chimeric-antigen-receptor-car-il-21-secretion-and-deleted-tgf-betar2-and-nr3c1-in-recurrent-glioblastoma-100637386","NCT07579208","A Phase1 Clinical Trial Evaluating Locoregional Delivery Of Engineered NK Cells Containing IL13Ra And EGFvIII Chimeric Antigen Receptor (CAR), IL-21 Secretion And Deleted TGF-BetaR2 And NR3C1 In Recurrent Glioblastoma","Eligibility Criteria\n\n1. Male or female subjects aged ≥ 18 years.\n2. Histologically confirmed supratentorial 2021 World Health Organization recurrent glioblastoma (IDH-wildtype GBM), gliosarcoma, or recurrent IDH-mutant WHO grade 4 astrocytoma, with any prior number of recurrences.\n3. Have received prior radiation and temozolomide therapy.\n4. Single tumor no larger than 5 cm in its greatest diameter.\n5. Karnofsky Performance Status (KPS) score of \\>70.\n6. Has a baseline brain MRI obtained no more than 30 days prior to NK cell infusion\n7. Adequate hematological function defined by white blood cell (WBC) count ≥ 3 x 10\u002FL with absolute neutrophil count (ANC) ≥1.5 x109\u002FL, lymphocyte count ≥ 0.5 x 109\u002FL, platelet count ≥ 100 x 109\u002FL, and Hgb ≥ 9 g\u002F dL (in absence of blood transfusion).\n8. Adequate hepatic function defined by a total bilirubin level . 1.5 \\~ ULN, an AST level ≤ 2.5 x ULN, and an ALT level ≤ 2.5 x ULN, and INR ≤ 1.5.\n9. Adequate renal function defined by creatinine ≤ 1.5 X upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL\u002Fmin for subject with creatinine levels \\> 1.5 X institutional ULN.\n10. Female subject of childbearing potential should have a negative serum pregnancy test. Subjects and their partners must be willing to use effective birth control during the study and for up to 3 months following last administration of NK cells. .\n11. Prior Avastin use is allowed after at least a 12-week washout period.\n12. Agree to sign consent to the long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.\n\nExclusion Criteria\n\n1. Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery.\n2. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks since last dose of agent administration.\n3. Has known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v5.0), any history of anaphylaxis, within 5 months.\n4. Has a known history of Human Immunodeficiency Virus (HIV) (positive HIV 1\u002F2 antibodies); HTLV1 and\u002For HTLV2; active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected). Participants with prior HBV vaccination (anti-HBs positive, HBsAg negative, anti-HBc negative) will NOT be excluded.\n5. Has a diagnosis of immunodeficiency or is receiving any immunosuppressive therapy (such as tacrolimus, cyclosporine, infliximab) within 7 days prior to study registration.\n6. Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study Day 0 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent such as thrombocytopenia or platelets toxicity. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study at the discretion of the treating investigator.\n7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include superficial tumors considered adequately treated locally with curative intent, including but not limited to basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Any exceptions must be discussed with the protocol PI.\n8. Has known Gliomatous meningitis or extracranial disease, or tumor localized primarily to the brainstem or spinal cord\n9. Midline shift greater than 0.5 cm or pending herniation\n10. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma\u002Fatopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Participants receiving epidural steroid injections for pain will be excluded. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.\n11. Has evidence of interstitial lung disease or active, non-infectious pneumonitis\n12. Has an active infection requiring systemic therapy or that in the opinion of the PI may interfere with the subject's participation, assessment of experimental treatment toxicity or increase the subject's risk of side effects\n13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate in the opinion of the treating investigator.\n14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n15. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit and through 3 months after last dose of the study treatment\n16. Has received a live vaccine within 30 days prior to the first dose of trial treatment\n17. Has a contraindication for undergoing MRIs\n18. Has evidence of bleeding diathesis or coagulopathy\n19. Is on full dose anticoagulants or antiplatelet therapy that cannot be held (full dose depends on the actual anticoagulant)\n20. Has significant hemorrhage on baseline scan defined as \\>1 cm diameter of acute blood\n21. Has received any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant)\n22. Has multifocal disease. Subject has multifocal GBM, defined as discrete sites of contrast enhancing disease without contiguous T2\u002FFLAIR abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2\u002FFLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted.",{"count":185,"type":22},[60],"To find the best method of administering NK cells in patients with recurrent glioblastoma.",[529,530,531,65,532,533,29],"Phase 1","NK Cell","IL13Ra","Chimera Antigen Receptor (CAR)","NR3C1","2026-05-06",{"date":536,"type":40},"2026-05-12",{"date":538,"type":22},"2026-10-24",{"date":540,"type":22},"2030-07-30",{"name":364,"class":74},{"id":543,"slug":544,"hasResults":12,"nctId":545,"briefTitle":546,"officialTitle":547,"acronym":4,"eligibilityCriteria":548,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":245,"enrollmentInfo":549,"targetDuration":4,"studyType":23,"phases":551,"briefSummary":552,"conditions":553,"keywords":554,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":560,"lastUpdatePostDateStruct":561,"startDateStruct":563,"completionDateStruct":565,"leadSponsor":567,"locationsCount":569},"100615792","phase-2-a-clinical-trial-testing-the-safety-of-the-investigational-drug-pumitamig-bnt327-and-how-well-it-works-in-patients-with-recurrent-glioblastoma-100615792","NCT07297212","A Clinical Trial Testing the Safety of the Investigational Drug Pumitamig (BNT327) and How Well it Works in Patients With Recurrent Glioblastoma","A Phase II, Multi-site, Open-label Trial Evaluating the Safety and Efficacy of Pumitamig and Bevacizumab as Monotherapy and Pumitamig in Combination With Temozolomide in Patients With Recurrent Glioblastoma","Key Inclusion Criteria:\n\n* Adults, aged 18-75 years inclusive at the time of giving informed consent. Local laws will be followed if the age at consent is older.\n* Have a histologically confirmed diagnosis of WHO Grade IV GBM, IDH-wildtype consistent with WHO CNS 2021 criteria.\n* Have recurrent supratentorial GBM who have received prior treatment with at least radiotherapy and temozolomide.\n* Have first recurrence documented by magnetic resonance imaging (MRI), with an interval of at least 12 weeks after the end of prior radiotherapy unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field.\n* Have been clinically evaluated as having relapsed or progressed disease with at least one measurable lesion as the targeted lesion based on RANO 2.0 criteria.\n* Have KPS ≥60.\n* Can swallow the medication and maintain oral administration.\n* Have a baseline brain MRI, not more than 14 days before starting the study treatment.\n* Have a stable dose of steroids ≥7 days before the contrast-enhanced scan.\n* Have adequate organ function, as defined in the protocol.\n\nKey Exclusion Criteria:\n\n* Have received any of the following therapies or drugs before study enrollment:\n\n  * Any anticancer therapies, including systemic, palliative, biologic, immunostimulatory, or immunosuppressive treatment within 4 weeks (or five half-lives, whichever is longer) before starting the study treatment.\n  * PD(L)-1\u002FVEGF bispecific antibodies, cluster of differentiation (CD)137 agonists or other immune checkpoint blockade therapies including monotherapy with either category or combinations thereof.\n  * Systemic corticosteroids (at a dosage greater than 2 mg\u002Fday of dexamethasone or an equivalent dose of other corticosteroids) within 7 days before starting the study treatment.\n  * Vaccinations with live attenuated vaccine(s) within 4 weeks before starting the study treatment.\n  * Broad-spectrum intravenous antibiotics therapy within 2 weeks before starting the study treatment.\n  * Any non-study investigational medicinal product within five half-lives of the first dose or within 4 weeks, whichever is longer, before starting the study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.\n  * Antiplatelet drugs, such as aspirin (\\>325 mg\u002Fday), clopidogrel (\\>75 mg\u002Fday), dipyridamole, ticlopidine or cilostazol, etc., within 10 days before starting the study treatment to avoid inclusion of participants who have used platelet aggregation inhibitors before the study.\n* Have had more than one recurrence of GBM.\n* Are allergic to dacarbazine and temozolomide.\n* Have known leptomeningeal disease, extracranial disease, or multicentric disease.\n* Have been diagnosed with secondary GBM (i.e., glioblastomas that progress from low grade diffuse astrocytoma or anaplastic astrocytoma).\n* Have previously received radiotherapy with anything other than standard radiotherapy (i.e., focally directed radiation).\n* Have received prior interstitial brachytherapy, interstitial thermal therapy, implanted chemotherapy, or therapeutics delivered by local injection or convection-enhanced drug delivery. Participants who had prior treatment with Gliadel® wafers and who had concurrent use of devices such as Tumor Treating Fields are excluded.\n* Have uncontrolled hypertension or poorly controlled diabetic conditions as specified in the protocol before study enrollment.\n* Are unable (due to existent medical condition, e.g., pacemaker or implantable cardioverter defibrillator device) or unwilling to have a head contrast-enhanced MRI.\n* Have undergone major surgery, open biopsy, or significant traumatic injury within 28 days before starting the study treatment, or a planned\u002Fanticipated need for major surgery during the study treatment period. Placement of vascular infusion devices is allowed. Note: If participant has had major surgery, they must have recovered adequately from the toxicity and\u002For complications from the treatment prior to the initiation of study treatment.\n* Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.\n* Have had other malignant tumors within 5 years before starting the study treatment. Exception: those who have been cured with local treatment (such as basal cell or squamous-cell carcinoma of the skin, superficial or noninvasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary carcinoma of thyroid and early-stage prostate cancer).\n* Have any of the following heart conditions within 6 months before starting the study treatment:\n\n  * Myocardial infarction, unstable angina, acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, cerebrovascular accident or other Grade 3 and above cardiovascular events.\n  * New York Heart Association functional classification ≥II heart failure or left ventricular ejection fraction \\\u003C50%.\n  * Ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, or congenital long QT syndrome. Participants with stable treated cardiac arrythmia\u002Fatrial fibrillation are allowed.\n  * Mean QTcF \\>480 ms (the electrocardiogram can be repeated at the discretion of the investigator).\n  * Cardiac troponin I or T \\>2 × upper limit normal.\n* Have serious or non-healing wounds, ulcers, or (incompletely healed) bone fracture. This includes history (within 6 months before starting the study treatment) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess or esophageal and gastric varices, or acute gastrointestinal bleeding. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation\u002Ffistula and\u002For the underlying process causing the fistula\u002Fperforation.\n* Have significant risk of hemorrhage (in the opinion of the investigator) or evidence of major coagulation disorders.\n* Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). However, participants who are clinically stable following treatment for these conditions (including therapeutic thoracentesis or paracentesis or with indwelling catheters, e.g., PleurX) are allowed.\n* Have adverse events from prior antitumor therapy that have not returned to Grade 1 (graded by CTCAE v5.0 criteria) or below (unless the investigator determines that certain adverse events pose no safety risk to participants, such as hair loss or stable hypothyroidism under hormone replacement therapy).\n* Active colitis, including infectious, radioactive, ischemic enteritis, within 4 weeks before starting the study treatment.\n* History of serious allergic diseases, history of serious allergy to drugs (including unlisted investigational drug) or known allergy or intolerance to any ingredient of the study treatment.\n* Uncontrolled seizures after best medical therapy or other neurological conditions including clinically significant autoimmune neurological disorders which can increase risk for adverse effects or confound assessment of study outcomes as determined by the investigator.\n* Have superior vena cava syndrome or symptoms of spinal cord compression.\n* Have active, or a history of, pneumonitis requiring treatment with steroids, or have active or a history of interstitial lung disease.\n* Have a known history of tuberculosis that was not successfully treated.\n\nNOTE: Other protocol defined Inclusion\u002FExclusion criteria apply.",{"count":550,"type":22},75,[163],"This multi-site Phase II study will enroll adults with histologically confirmed diagnosis of World Health Organization (WHO) Grade IV glioblastoma (GBM), isocitrate dehydrogenase (IDH)-wildtype consistent with WHO central nervous system (CNS) 2021 criteria who have received prior first-line treatment including with at least radiotherapy and temozolomide, with a Karnofsky performance status (KPS) ≥60, adequate organ function, and at least one measurable lesion according to the response assessment in neuro-oncology (RANO) 2.0 criteria.",[29],[555,120,556,557,558,559],"Bispecific antibody","Immunotherapy in combination with chemotherapy","Brain tumor","Programmed death-ligand 1 (PD-L1)","Vascular endothelial growth factor(-A) (VEGF-A)","2026-04-28",{"date":562,"type":40},"2026-04-29",{"date":564,"type":40},"2026-01-15",{"date":566,"type":22},"2029-07",{"name":568,"class":47},"BioNTech SE",6,{"id":571,"slug":572,"hasResults":12,"nctId":573,"briefTitle":574,"officialTitle":575,"acronym":576,"eligibilityCriteria":577,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":440,"enrollmentInfo":578,"targetDuration":4,"studyType":23,"phases":580,"briefSummary":581,"conditions":582,"keywords":583,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":588,"lastUpdatePostDateStruct":589,"startDateStruct":590,"completionDateStruct":592,"leadSponsor":594,"locationsCount":75},"100519143","phase-1-sonodynamic-therapy-in-patients-with-recurrent-gbm-100519143","NCT06039709","Sonodynamic Therapy in Patients With Recurrent GBM","Pilot Study of Sonodynamic Therapy With 5-ALA for the Treatment of Recurrent Glioblastoma Using Neuronavigation-Guided Low-Intensity Focused Ultrasound","GBM 001","Inclusion Criteria:\n\n1. Disease status and Disease Parameters:\n\n   * Suspected recurrent glioblastoma that is clearly measurable based on the modified Response Assessment in Neuro-Oncology (RANO) criteria\n   * The tumor lesion needs to comprise at least 1 contrast-enhancing lesion with a volume of ≥ 2 cm3 and ≤ 20 cm3 of targeted treatment area\n   * Tumor tissue to be treated is in a surgically accessible brain region for resection\n   * The brain tumor to be treated must be in the treatment envelope of the NaviFUS system (30 mm to 90 mm from the inner skull table)\n   * Recurrence will be assessed by imaging and confirmed by consensus at tumor board\n2. Men or women between the ages of 18-80 years of age at the time of consent\n3. No contraindication to repeat brain surgery\n4. Karnofsky Performance Score of 70-100\n5. Able to undergo an MRI with contrast\n6. Able to swallow oral medications\n7. Willingness and ability to comply with scheduled visits, treatment plans, lifestyle considerations, laboratory tests, and other procedures.\n8. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).\n9. Participants who received prior chemotherapy, radiation therapy, immunotherapy, and\u002For another investigational therapy must have recovered (Common Terminology Criteria for Adverse Events \\[CTCAE\\] Grade ≤1 or baseline) from the acute effects of the therapy or therapies) except for residual alopecia or Grade 2 peripheral neuropathy prior to registration.\n10. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):\n\nHematological\n\n* Absolute neutrophil count (ANC) ≥1000\u002Fmm3\n* Platelets ≥ 100,000\u002Fmm3\n* Hemoglobin ≥ 11 g\u002FdL for women and ≥ 12 g\u002FdL for men Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator.\n* INR ≤ 1.4\n\nRenal \\& Hepatic\n\n* Creatinine clearance CrCl ≥ 60 mL\u002Fmin\u002F1.73 m2 as estimated by the Cockcroft-Gault (C-G) equation. If estimated CrCl is abnormal, accurate measurement should be obtained by 24- hour CrCl.\n* Bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 2.0x ULN is allowed).\n* AST and ALT ≤ 3 x ULN\n* Alkaline phosphatase ≤ 3 x ULN\n* Estimated glomerular filtration rate ≥30mL\u002Fmin\u002F1.73m2\n\nExclusion Criteria:\n\n1. Known sensitivity or allergy to 5-ALA\n2. Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts)\n3. Diagnosis of porphyria\n4. Hypersensitivity against porphyrins\n5. Pregnancy\n6. Significant cardiac disease or coagulopathy\n7. Herniation \u002F intractable seizure \u002F other clinical indications requiring urgent resection\n8. Known active systemic bacterial infection (requiring intravenous \\[IV\\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C (for example, hepatitis B surface antigen positive)\n9. Have had a recent (≤3 months prior to registration) transient ischemic attack or stroke\n10. Significant vascular disease (e.g. aortic aneurysm)\n11. Evidence of bleeding diathesis or coagulopathy\n12. Need for systemic anticoagulation which cannot be held for 7 days prior to SDT\n13. Unstable angina and\u002For congestive heart failure (NYH Class III or Class IV; see section 13.2) within 6 months prior to registration\n14. Severe hypertension (systolic ≥ 180 mm Hg; diastolic ≥ 120 mm Hg) despite anti-hypertensive medications\n15. Transmural myocardial infarction within 6 months prior to registration\n16. Serious and inadequately controlled cardiac arrhythmia\n17. Acute exacerbation of chronic obstructive pulmonary disease\n18. Has serious and\u002For uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study\n19. Treatment with another investigational drug or investigational procedure within 30 days prior to registration or within 5 half-lives of the investigational product, whichever is longer\n20. Brain edema and\u002For mass effect that causes midline shift of more than 15 mm\n21. Evidence of recent (within 30 days prior to registration) intracranial hemorrhage\n22. Calcifications or metallic implanted objects in the focused ultrasound sonication path\n23. Scalp atrophy or scars at the expected location of transducer\n24. Cerebral or systemic vasculopathy\n25. Need for or currently on dialysis\n26. Respiratory: chronic pulmonary disorders (e.g., severe emphysema, COPD, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area).\n27. Receipt of radiotherapy ≤21 days prior to registration\n28. Receipt of chemotherapy ≤ 21 days prior to registration\n29. Prior treatment with sonodynamic therapy\n30. Concurrent use of Optune device\n31. Concurrent use of supplements or medications with substantial antioxidant effects (including sulfhydryl-containing medications such as captopril or supplements such as N-acetylcysteine, or high doses of vitamins with antioxidant activity such as C or E)\n32. Known sensitivity to gadolinium",{"count":579,"type":22},11,[60],"Patients diagnosed with glioblastoma (GBM) are faced with limited treatment options. This pilot study will evaluate the safety and feasibility of combining an investigational drug called 5-ALA with neuronavigation-guided low-intensity focused ultrasound (LIFU) for patients who have recurrent GBM. Focused ultrasound (FUS) can be used to non-invasively destroy tumor tissue while preserving normal tissue. When FUS is combined with 5-ALA, this combinatorial approach is called sonodynamic therapy (SDT), and this investigational therapy is being tested for its ability to cause damage to GBM cells. SDT will take place prior to surgery for recurrent GBM.",[29,189,30],[584,585,586,587,221],"Sonodynamic Therapy","Low-Intensity Focused Ultrasound (LIFU)","Focused Ultrasound","5-ALA","2026-04-27",{"date":560,"type":40},{"date":591,"type":40},"2024-01-31",{"date":593,"type":22},"2027-06",{"name":595,"class":74},"Shayan Moosa, MD",{"id":597,"slug":598,"hasResults":12,"nctId":599,"briefTitle":600,"officialTitle":601,"acronym":4,"eligibilityCriteria":602,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":245,"enrollmentInfo":603,"targetDuration":4,"studyType":23,"phases":604,"briefSummary":605,"conditions":606,"keywords":609,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":619,"lastUpdatePostDateStruct":620,"startDateStruct":622,"completionDateStruct":624,"leadSponsor":626,"locationsCount":75},"100635334","phase-1-dual-targeting-car-nk-cells-for-recurrentprogressive-glioblastoma-and-high-grade-glioma-100635334","NCT07551336","Dual-Targeting CAR-NK Cells for Recurrent\u002FProgressive Glioblastoma and High-Grade Glioma","A Phase 1, First-in-Human, Biomarker-Guided, Dose-Escalation and Expansion Study of Locoregional Dual-Targeting CAR-NK Cells Directed Against IL13Rα2, EGFR\u002FEGFRvIII, and\u002For B7-H3 (CD276) in Adults With Recurrent or Progressive Glioblastoma or High-Grade Glioma","Inclusion Criteria:\n\n* Age 18 to 75 years at the time of consent.\n* Histologically confirmed glioblastoma (WHO grade 4) or diffuse high-grade glioma (WHO grade 3 or 4) that is recurrent or progressive after standard therapy.\n* Planned clinically indicated tumor resection or stereotactic biopsy (or availability of adequate archived tumor tissue) to support antigen testing and locoregional catheter placement.\n* Tumor demonstrates expression of at least two of the following antigens above protocol-defined thresholds: IL13Rα2, EGFR (wild-type) and\u002For EGFRvIII, B7-H3 (CD276).\n* Karnofsky Performance Status (KPS) ≥ 60.\n* Adequate organ function (hematologic, renal, hepatic) as defined by protocol laboratory criteria.\n* Ability to undergo brain MRI with contrast (unless contraindicated and alternative imaging is permitted).\n* Negative pregnancy test for women of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined period after infusion.\n* Ability to understand and willingness to sign informed consent.\n\nExclusion Criteria:\n\n* Active, uncontrolled infection (including uncontrolled bacterial, viral, or fungal infection).\n* Known HIV infection with uncontrolled viral load; active hepatitis B or hepatitis C with detectable viral load (unless permitted per protocol).\n* Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.\n* Requirement for high-dose systemic corticosteroids (e.g., \\>4 mg\u002Fday dexamethasone equivalent) within 7 days prior to lymphodepletion\u002Finfusion (physiologic replacement permitted).\n* Prior gene-modified cellular therapy (e.g., prior CAR-T\u002FCAR-NK) within 6 months, or prior therapy targeting IL13Rα2, EGFR\u002FEGFRvIII, or B7-H3 where residual engineered cells could confound safety assessments.\n* Diffuse leptomeningeal disease as the only site of disease, or anatomy that precludes safe catheter placement (unless specifically allowed by protocol).\n* Uncontrolled seizures despite optimal medical therapy.\n* Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia) that would increase risk with lymphodepletion or infusion procedures.\n* Pregnant or breastfeeding.\n* Any condition that, in the investigator's judgment, would make the participant unsuitable for the study or could interfere with protocol adherence.",{"count":185,"type":22},[60],"This is a draft, ClinicalTrials.gov-style example record for a first-in-human Phase 1 study evaluating locoregional administration of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in adults with recurrent or progressive glioblastoma (GBM) or other high-grade glioma (HGG). Participants will undergo tumor antigen profiling for IL13Rα2, EGFR\u002FEGFRvIII, and B7-H3 (CD276). Based on this assessment, each participant will receive the most suitable dual-target CAR construct to reduce antigen-escape risk.",[377,607,28,608,29],"High-Grade Gliomas","Recurrent High-Grade Gliomas",[610,611,612,613,614,65,615,616,617,618],"CAR-NK","Dual targeting","Biomarker-guided","IL13Rα2","EGFR","B7-H3 (CD276)","Locoregional","Intracavitary","Ommaya reservoir","2026-04-18",{"date":621,"type":40},"2026-04-24",{"date":623,"type":40},"2026-03-02",{"date":625,"type":22},"2028-04-17",{"name":627,"class":47},"Beijing Biotech",{"id":629,"slug":630,"hasResults":12,"nctId":631,"briefTitle":632,"officialTitle":633,"acronym":4,"eligibilityCriteria":634,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":635,"targetDuration":4,"studyType":23,"phases":636,"briefSummary":637,"conditions":638,"keywords":639,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":643,"lastUpdatePostDateStruct":644,"startDateStruct":646,"completionDateStruct":648,"leadSponsor":650,"locationsCount":75},"100634318","early-phase-1-evaluating-safety-tolerability-and-preliminary-efficacy-of-ysch-01-monotherapy-and-in-combination-with-atezolizumab-for-recurrent-glioblastoma-100634318","NCT07538128","Evaluating Safety, Tolerability, and Preliminary Efficacy of YSCH-01 Monotherapy and in Combination With Atezolizumab for Recurrent Glioblastoma","An Open-Label, Single-Center, Multiple-Dose Exploratory Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of YSCH-01 Monotherapy and in Combination With Atezolizumab in the Treatment of Recurrent Glioblastoma","Inclusion Criteria\n\nParticipants must meet all the following criteria to be enrolled in this study:\n\n1. Age \\> 18 years, male or female.\n2. Expected survival ≥ 12 weeks.\n3. Karnofsky Performance Status (KPS) score ≥ 70 at baseline.\n4. Histopathologically confirmed glioblastoma (GBM), with first recurrence after prior surgery, chemotherapy, and\u002For radiotherapy.\n5. Presence of 1 contrast-enhancing tumor lesion (diameter 1-4 cm) assessed by MRI during the screening phase.\n6. Eligibility for tumor biopsy and Ommaya reservoir implantation based on hematological, hepatic, renal, and coagulation function parameters.\n7. Recovery from toxic effects of prior chemo\u002Fradiotherapy (CTCAE ≤ Grade 1, except for special cases like alopecia or pigmentation), with the Investigator determining that the corresponding adverse events (AEs) pose no safety risk.\n8. Eligible subjects of reproductive potential (male and female) must agree to use effective contraception during the trial and for at least 6 months after the last dose.\n\nExclusion Criteria\n\nParticipants with any of the following conditions are ineligible for enrollment:\n\n1. History or current evidence of another primary malignancy.\n2. Known allergy to the study drug or any of its excipients, or a history of unexplained severe allergic reactions.\n3. Any contraindication to gadolinium-enhanced MRI, such as presence of a pacemaker, infusion pump, or allergy to MRI contrast agents.\n4. Tumor involvement of the brainstem, cerebellum, or spinal cord; or leptomeningeal disease.\n5. MRI evidence of tumor enhancement extending to the ventricular wall, or the tumor cavity is fused with the ventricle after surgery.\n6. Preoperative MRI assessment showing the Ommaya puncture path traverses the ventricles.\n7. Active infection requiring intravenous antibiotic therapy, or unexplained fever (body temperature ≥37.5°C).\n8. Uncontrolled systemic diseases or relevant medical history, including: diabetes mellitus, cardiovascular\u002Fcerebrovascular disease (e.g., heart failure ≥NYHA Class II, hypertension ≥Grade 2, ≥First-degree atrioventricular block, history of myocardial infarction, myocarditis), pulmonary insufficiency, thyroid dysfunction, cerebral infarction within the past 6 months.\n9. Active autoimmune disease or history of autoimmune disorders (e.g., ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune vasculitis, Wegener's granulomatosis).\n10. Plan or requirement to receive any live vaccine during the screening or treatment phase.\n11. Other conditions assessed as incompatible with intravenous administration of Atezolizumab.",{"count":293,"type":22},[323],"The clinical study of YSCH-01 will adopt an open-label, randomized design, with a planned enrollment of 10 participants with recurrent glioblastoma. Participants will be randomly allocated to the YSCH-01 monotherapy cohort or the YSCH-01 + Atezolizumab combination cohort, with 5 participants in each cohort. The study consists of the following three phases: screening phase, treatment phase, and follow-up phase. The primary endpoint is the 1-year survival rate of participants",[29],[640,29,641,642],"YSCH-01","Adenovirus","Atezolizumab","2026-04-13",{"date":645,"type":40},"2026-04-20",{"date":647,"type":40},"2025-01-09",{"date":649,"type":22},"2027-02-28",{"name":651,"class":74},"Huashan Hospital",{"id":653,"slug":654,"hasResults":12,"nctId":655,"briefTitle":656,"officialTitle":657,"acronym":4,"eligibilityCriteria":658,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":4,"enrollmentInfo":659,"targetDuration":4,"studyType":23,"phases":661,"briefSummary":662,"conditions":663,"keywords":664,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":668,"lastUpdatePostDateStruct":669,"startDateStruct":671,"completionDateStruct":673,"leadSponsor":675,"locationsCount":311},"100405427","phase-2-sacituzumab-govitecan-in-recurrent-glioblastoma-100405427","NCT04559230","Sacituzumab Govitecan in Recurrent Glioblastoma","A Phase II, Multicenter, Prospective Study of Sacituzumab Govitecan in Recurrent Glioblastoma","Inclusion Criteria:\n\n1. At least 18 years of age.\n2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB\u002FEthics Committee.\n3. Histologically confirmed IDH wild type (primary) GBM. Molecular GBM (as per cIMPACT-NOW 3) is allowed as is gliosarcoma and epithelioid glioblastoma. IDH-mutant glioma is not allowed.\n4. Progression following standard combined modality treatment with radiation and temozolomide chemotherapy if O6-Methylguanine-DNA Methyltransferase (MGMT) methylated.\n\n   * Prior temozolomide is not required for MGMT unmethylated, but patient must have received standard doses of radiation.\n   * Inclusion of additional investigational therapy with standard frontline therapy is not exclusionary. No additional lines of therapy given for recurrent disease.\n   * Prior tumor-treating field therapy is not excluded, nor considered and additional line of therapy as this is often given concurrently with other therapy lines.\n5. Patients may have had been operated for recurrence, but if operated must have had surgery a minimum of 2 weeks prior to enrollment and have an MRI completed within 48 hours following surgery.\n6. No radiotherapy within the 3 months prior to the diagnosis of progression.\n7. Willingness to forego tumor-treatment field (Optune) therapy during participation in the study.\n8. Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.\n9. Recovered from toxicities of prior therapy to grade 0 or 1, except for neuropathy (Grade ≤2) and alopecia.\n10. ECOG performance status ≤ 2.\n11. Life expectancy of at least 6 months.\n12. Acceptable liver function:\n\n    * Bilirubin ≤ 1.5 times upper limit of normal\n    * AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN)\n13. Acceptable renal function:\n\n    • Creatinine clearance ≥30 mL\u002Fminute according to the Cockcroft and Gault formula\n14. Acceptable hematologic status (without hematologic support):\n\n    * ANC ≥1500 cells\u002FuL\n    * Platelet count ≥100,000\u002FuL\n    * Hemoglobin ≥9.0 g\u002FdL\n15. All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.\n16. Availability of biological material for central review and biomarker evaluation.\n17. Untreated recurrent or residual disease that is measurable by RANO criteria at time of enrollment. Multifocal and infratentorial disease is allowed.\n18. Positive Trop-2 expression (H-Score ≥200), as verified by central review at University of Texas Health Science Center at San Antonio (UTHSA).\n\nExclusion Criteria:\n\n1. Prior treatment with bevacizumab or other VEGF inhibitors or VEGF-Receptor signaling inhibitors\n2. The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.\n\n3 The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.\n\n4\\. The subject is unable to undergo MRI scan (eg, has pacemaker). 5. The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).\n\n6\\. The subject is pregnant or breast-feeding. 7. The subject has serious intercurrent illness, such as:\n\n* hypertension (two or more blood pressure \\[BP\\] readings performed at screening of \\> 150 mmHg systolic or \\> 100 mmHg diastolic) despite optimal treatment\n* non-healing wound, ulcer, or bone fracture\n* significant cardiac arrhythmias\n* untreated hypothyroidism\n* unhealed rectal or peri-rectal abscess\n* uncontrolled active infection\n* symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug\n* any history of cardiac arrhythmia or heart block\n* stroke or transient ischemic attack within 6 months 8. The subject has received any of the following prior anticancer therapy:\n* Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed\n* Systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug\n* Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug\n* Nitrosoureas or mitomycin C within 42 days, or metronomic\u002Fprotracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug\n* Prior treatment with carmustine wafers 9. Patients with radiographically or clinically apparent leptomeningeal involvement are excluded.",{"count":660,"type":22},32,[163],"This is an open-label single arm study. All patients will receive the study drug. The aim of the study is to compare overall survival (OS) of patients with recurrent brain tumor, known as Glioblastoma (GBM) having high levels of a protein, Trophoblast cell surface antigen 2 (Trop-2), expression on treatment with Sacituzumab Govitecan (SG) versus lomustine only which has been used in the past.",[29],[665,666,667],"Trophoblast Cell-Surface Antigen 2","Trop-2","Sacituzumab Govitecan","2026-03-26",{"date":670,"type":40},"2026-03-30",{"date":672,"type":40},"2022-01-06",{"date":674,"type":22},"2028-02",{"name":676,"class":74},"The University of Texas Health Science Center at San Antonio"]