[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"undifferentiated-sarcoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:undifferentiated-sarcoma":58},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,83,118],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":4,"maxAge":16,"enrollmentInfo":17,"targetDuration":4,"studyType":20,"phases":21,"briefSummary":24,"conditions":25,"keywords":68,"overallStatus":70,"whyStopped":4,"lastUpdateSubmitDate":71,"lastUpdatePostDateStruct":72,"startDateStruct":75,"completionDateStruct":77,"leadSponsor":79,"locationsCount":82},"100534472","phase-1-nrsts2021-a-risk-adapted-study-evaluating-maintenance-pazopanib-limited-margin-dose-escalated-radiation-therapy-and-selinexor-in-non-rhabdomyosarcoma-soft-tissue-sarcoma-nrsts-100534472",false,"NCT06239272","NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)","Inclusion Criteria:\n\nInclusion Criteria - All Patients\n\n* Patients must be 1-30 years at the time of the biopsy that established the diagnosis of NRSTS.\n* Surgical Resection: Patients who had an upfront resection prior to enrollment will be eligible if they are able to begin therapy within 28 days of resection assuming other eligibility criteria are met. Delayed resection is preferred for all patients with intermediate and high-risk disease.\n* Lansky performance status score ≥ 60 for patients ≤ 16 years of age. Karnofsky performance status score ≥ 60 for patients \\>16 years of age. Note patients 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\nDiagnosis\n\n• Patients with CIC-DUX 4 rearranged sarcomas will be enrolled on the high-risk stratum only, regardless of presence of metastasis, size, or resection status.\n\nPatient has low-risk disease if the patient has a:\n\n* Low-grade tumor of any size where R0 or R1 surgical margins are anticipated or achieved.\n* High-grade tumors that are \\\u003C 5 cm where R0 or R1 resection margins are anticipated or achieved.\n\nPatient must have adequate organ function in the organs that will be within the radiotherapy field.\n\nAdequate renal function defined as:\n\n* Creatinine clearance or radioisotope GFR \\> 70 mL\u002Fmin\u002F1.73 m2, or\n* A normal serum creatinine based on age\u002Fgender as follows\n\nAge Maximum Serum Creatinine (mg\u002FdL) Male Female 2 to \\\u003C 6 years 0.8 0.8 6 to \\\u003C 10 years 1 1 10 to \\\u003C 13 years 1.2 1.2 13 to \\\u003C 16 years 1.5 1.4 \\> 16 years 1.5 1.4\n\nAdequate liver function defined as:\n\n* Total bilirubin \\\u003C 1.5 x upper limit of normal (ULN) for age\n* SGOT (AST) or SGPT (ALT) \\\u003C 2.5 x ULN for age\n\nAdequate cardiac function defined as:\n\n* Ejection fraction of \\> 55% by echocardiogram or cardiac MRI\n* QTc \\\u003C 480 msec\n\nAdequate pulmonary function defined as:\n\n* No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading \\> 94% on room air if there is clinical indication for determination.\n\nInclusion Criteria - Intermediate and High Risk Participants\n\nPatient has intermediate-risk if the patient has a:\n\n* Low-grade non-metastatic initially unresectable disease at study enrollment where delayed resection is planned.\n* High-grade \\\u003C 5 cm non-metastatic initially unresectable disease at study enrollment where delayed resection is planned. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is planned are eligible for this arm.\n* High-grade tumor \\> 5 cm that is potentially resectable.\n\nPatient high-risk if the patient has:\n\n* Metastatic disease at presentation\n* Unresectable disease at study enrollment where delayed resection is not anticipated. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is not-planned are eligible for this arm.\n* CIC-DUX4 rearranged sarcoma\n\nOrgan Function\n\nAdequate bone marrow function defined as:\n\n* Absolute neutrophil count \\> 1000\u002FµL\n* Platelet count \\> 100,000\u002FµL\n* Hemoglobin \\> 8 g\u002FdL for patients \\\u003C 16 years of age\n* Hemoglobin \\> 9 g\u002FdL for patients \\> 16 years of age\n\nNote: No transfusions are permitted 7 days prior to laboratory studies to determine eligibility.\n\nAdequate renal function defined as:\n\n* Creatinine clearance or radioisotope GFR \\> 70 mL\u002Fmin\u002F1.73 m2, or\n* A normal serum creatinine based on age\u002Fgender as follows\n\nAge Maximum Serum Creatinine (mg\u002FdL) Male Female 2 to \\\u003C 6 years 0.8 0.8 6 to \\\u003C 10 years 1 1 10 to \\\u003C 13 years 1.2 1.2 13 to \\\u003C 16 years 1.5 1.4 \\> 16 years 1.5 1.4\n\nAdequate liver function defined as:\n\n* Total bilirubin \\\u003C 1.5 x upper limit of normal (ULN) for age\n* SGOT (AST) or SGPT (ALT) \\\u003C 2.5 x ULN for age\n\nAdequate cardiac function defined as:\n\n* Ejection fraction of \\> 55% by echocardiogram or cardiac MRI\n* QTc \\\u003C 480 msec\n\nAdequate pulmonary function defined as:\n\n* No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading \\> 94% on room air if there is clinical indication for determination.\n\nAnticoagulation\n\nPatients on low molecular weight heparin, warfarin (with a stable INR), or direct oral anticoagulants (DOAC) who have been on a stable dose of are eligible. Patients being treated for a pulmonary embolism or deep venous thrombosis (DVT) must have been treated for a minimum of 6 weeks prior to starting therapy treatment.\n\nLife Expectancy\n\nPatient must have a life expectancy of at least 3 months with appropriate therapy.\n\nExclusion Criteria:\n\n* Patients with known primary CNS sarcoma or CNS metastases are not eligible. Note: Brain imaging is not an eligibility requirement. Tumors with intracranial extension will be allowed.\n* Patients with the following histologic diagnosis are not eligible: intermediate locally aggressive tumors as defined by WHO, malignant rhabdoid tumor, alveolar soft part sarcoma, infantile fibrosarcoma, unresectable\u002Fmetastatic dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor, desmoid fibromatosis, rhabdomyosarcoma, desmoplastic small round cell tumor, BCOR-CCNB3 fusion positive sarcoma.\n* Bleeding diathesis: Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: Patients aged \\> 17 years with excess of 2.5 mL of hemoptysis are not eligible).\n* Uncontrolled hypertension: Patients with uncontrolled hypertension (CTCAE v5 Grade ≥ 2) are ineligible. Hypertension must be well controlled on stable doses of medication for at least two weeks.\n\nPrior Therapy\n\n* Patients must have had no prior systemic therapy for the treatment of the NRSTS\n* Patients must have had no prior anthracycline or ifosfamide chemotherapy\n* Patients must have had no prior use of pazopanib or similar multi-targeted TKI.\n\nPatients must have had no prior radiotherapy to tumor-involved sites.\n\nNote: Patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded.\n\n* CYP3A4 Substrates WITH Narrow Therapeutic Indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible. Note: the use of fentanyl is permitted.\n* CYP3A4 Inhibitors: Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin, many NNRTIs, diltiazem, verapamil, and grapefruit juice are not eligible.\n* CYP3A4 Inducers: Patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are not eligible (with the exception of glucocorticoids).\n* Certain medications that are associated with a risk for QTc prolongation and\u002For Torsade's de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible.\n* Subjects with any condition that may impair the ability to absorb oral medications\u002Finvestigational product including:\n\n  * prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel\n  * active peptic ulcer disease\n  * malabsorption syndrome\n\n3.4.12 Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 4 weeks prior to study enrollment.\n\n3.4.13 Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:\n\n* active peptic ulcer disease\n* known intraluminal metastatic lesions\n* inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation\n* history of abdominal fistula, gastrointestinal perforation or intra- abdominal abscess within 28 days prior to beginning study treatment.\n\n3.4.14 Pulmonary embolism or DVT. Patients must not have experienced:\n\n* An untreated pulmonary embolism or DVT in last 6 months or\n* treated pulmonary embolism or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks\n* arterial thrombosis in last 12 months\n\nHistory of serious or non-healing wound, ulcer, or bone fracture.\n\nUncontrolled 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\nHIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib. In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy.\n\nPatients who are receiving any other investigational agent(s).\n\nPregnancy and Breast Feeding\n\n* Pregnancy and Breast Feeding Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies.\n* Lactating females are not eligible unless they have agreed not to breastfeed their infants during treatment and for a period of 1 month following completion of treatment.\n* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.\n* Unwillingness to use an effective contraceptive method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with reproductive potential.","ALL","30 Years",{"count":18,"type":19},139,"ESTIMATED","INTERVENTIONAL",[22,23],"PHASE1","PHASE2","The study participant has been diagnosed with non-rhabdomyosarcoma (NRSTS).\n\nPrimary Objectives\n\nIntermediate-Risk\n\n* To estimate the 3-year event-free survival for intermediate-risk patients treated with ifosfamide, doxorubicin, pazopanib, surgery, and maintenance pazopanib, with or without RT.\n* To characterize the pharmacokinetics of pazopanib and doxorubicin in combination with ifosfamide in intermediate-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and pazopanib and doxorubicin pharmacokinetics.\n\nHigh-Risk\n\n* To estimate the maximum tolerated dose (MTD) and\u002For the recommended phase 2 dosage (RP2D) of selinexor in combination with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib in high-risk participants.\n* To characterize the pharmacokinetics of selinexor, pazopanib and doxorubicin in combination with ifosfamide in high-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and selinexor, pazopanib and doxorubicin pharmacokinetics.\n\nSecondary Objectives\n\n* To estimate the cumulative incidence of primary site local failure and distant metastasis-free, disease-free, event-free, and overall survival in participants treated on the risk-based treatment strategy defined in this protocol.\n* To define and describe the CTCAE Grade 3 or higher toxicities, and specific grade 1-2 toxicities, in low- and intermediate-risk participants.\n* To study the association between radiation dosimetry in participants receiving radiation therapy and the incidence and type of dosimetric local failure, normal adjacent tissue exposure, and musculoskeletal toxicity.\n* To evaluate the objective response rate (complete and partial response) after 3 cycles for high-risk patients receiving the combination of selinexor with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib.\n* To assess the relationship between the pharmacogenetic variation in drug-metabolizing enzymes or drug transporters and the pharmacokinetics of selinexor, pazopanib, and doxorubicin in intermediate- or high-risk patients.\n\nExploratory Objectives\n\n* To explore the correlation between radiographic response, pathologic response, survival, and toxicity, and tumor molecular characteristics, as assessed through next-generation sequencing (NGS), including whole genome sequencing (WGS), whole exome sequencing (WES), and RNA sequencing (RNAseq).\n* To explore the feasibility of determining DNA mutational signatures and homologous repair deficiency status in primary tumor samples and to explore the correlation between these molecular findings and the radiographic response, survival, and toxicity of patients treated on this protocol.\n* To explore the feasibility of obtaining DNA methylation profiling on pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to assess the correlation with this and pathologic diagnosis, tumor control, and survival outcomes where feasible.\n* To explore the feasibility of obtaining high resolution single-cell RNA sequencing of pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to characterize the longitudinal changes in tumor heterogeneity and tumor microenvironment.\n* To explore the feasibility of identifying characteristic alterations in non-rhabdomyosarcoma soft tissue sarcoma in cell-free DNA (cfDNA) in blood as a non-invasive method of detecting and tracking changes during therapy, and to assess the correlation of cfDNA and mutations in tumor samples.\n* To describe cardiovascular and musculoskeletal health, cardiopulmonary fitness among children and young adults with NRSTS treated on this protocol.\n* To investigate the potential prognostic value of serum cardiac biomarkers (high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro B-type natriuretic peptide (NT-Pro-BNP), serial electrocardiograms (EKGs), and serial echocardiograms in patients receiving ifosfamide, doxorubicin, and pazopanib, with or without selinexor.\n* To define the rates of near-complete pathologic response (\\>90% necrosis) and change in FDG PET maximum standard uptake value (SUVmax) from baseline to week 13 in intermediate risk patients with initially unresectable tumors treated with induction pazopanib, ifosfamide, and doxorubicin, and to correlate this change with tumor control and survival outcomes.\n* To determine the number of high-risk patients initially judged unresectable at diagnosis that are able to undergo primary tumor resection after treatment with ifosfamide, doxorubicin, selinexor, and pazopanib.\n* To identify the frequency with which assessment of volumes of interest (VOIs) of target lesions would alter RECIST response assessment compared with standard linear measurements.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67],"Adipocytic Neoplasm","Liposarcoma","Atypical Fibroxanthoma","Angiomatoid Fibrous Histiocytoma","Fibrosarcoma NOS","Myxofibrosarcoma","Angiosarcoma","Osteosarcoma, Extraskeletal","Dedifferentiated Liposarcoma","Myxoid Liposarcoma","Pleomorphic Liposarcoma","Myxoid Pleomorphic Liposarcoma","Low Grade Fibromyxoid Sarcoma","Sclerosing Epithelioid Fibrosarcoma","Malignant Tenosynovial Giant Cell Tumor of Soft Tissue","Epithelioid Hemangioendothelioma","Glomus Tumor","Inflammatory Leiomyosarcoma","Leiomyosarcoma","Ossifying Fibromyxoid Tumor, Malignant","Myoepithelioma","Synovial Sarcoma","Epithelioid Sarcoma","Perineurioma, Malignant","Clear Cell Sarcoma","Extraskeletal Myxoid Chondrosarcoma","Granular Cell Tumor, Malignant","Melanotic Malignant Nerve Sheath Tumor","Malignant Peripheral Nerve Sheath Tumor","Perivascular Epithelioid Tumor, Malignant","Intimal Sarcoma","Myoepithelial Carcinoma","Undifferentiated Sarcoma","Pleomorphic Sarcoma, Undifferentiated","Round Cell Sarcoma, Undifferentiated","NTRK-Rearranged Spindle Cell Neoplasm","Phosphaturic Mesenchymal Tumor, Malignant","Round Cell Sarcoma","Well Differentiated Liposarcoma","Giant Cell Tumor of Soft Parts NOS","Low Grade Myofibroblastic Sarcoma","Dermatofibrosarcoma Protuberans, Fibrosarcomatous",[69],"Proton therapy","RECRUITING","2026-07-31",{"date":73,"type":74},"2026-08-03","ACTUAL",{"date":76,"type":74},"2024-03-27",{"date":78,"type":19},"2037-06",{"name":80,"class":81},"St. Jude Children's Research Hospital","OTHER",7,{"id":84,"slug":85,"hasResults":11,"nctId":86,"briefTitle":87,"officialTitle":88,"acronym":89,"eligibilityCriteria":90,"healthyVolunteers":11,"sex":15,"minAge":91,"maxAge":4,"enrollmentInfo":92,"targetDuration":4,"studyType":20,"phases":94,"briefSummary":95,"conditions":96,"keywords":100,"overallStatus":70,"whyStopped":4,"lastUpdateSubmitDate":108,"lastUpdatePostDateStruct":109,"startDateStruct":111,"completionDateStruct":113,"leadSponsor":115,"locationsCount":117},"100509838","phase-1-lurbinectedin-in-fet-fused-tumors-100509838","NCT05918640","Lurbinectedin in FET-Fused Tumors","Lurbinectedin in FET-Fusion Tumors (LIFFT)","LiFFT","Inclusion Criteria:\n\n1. Age ≥ 10 years.\n2. Phase 1: Histological confirmed diagnosis of recurrent or relapsed solid tumor failing primary therapy. Patients must have a known FET fusion (fusion that contains EWSR1, FUS, or TAF15) as documented by next generation sequencing, polymerase chain reaction (PCR) or Fluorescence in situ hybridization (FISH). Patients with a histological diagnosis of Ewing sarcoma with EWS-FLI1 are eligible for dose escalation but not for the exploratory cohort. Please note patients with Ewing sarcoma and alternative FET-ETS fusions (including but not limited to EWS-ERG, EWS-ETV1, EWS-ETV4, EWS-FEV, FUS-ERG, FUS-FEV) are eligible for the exploratory cohort.\n3. Phase 2: Histologically confirmed diagnosis of recurrent or relapsed Ewing sarcoma failing primary therapy with confirmation of EWS-FLI1 fusion and breakpoint by Next generation sequencing or PCR or EWSR1 rearrangement confirmed by FISH and available tissue for central confirmation of EWS-FLI1 fusion and breakpoint.\n4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (age \\>16 years) or Lansky of at least 70 (age \\\u003C16 years).\n5. Disease status (baseline imaging must be performed within 28 days of Day 1 of study treatment):\n\n   1. Phase 1: At least one site of measurable disease on CT or MRI as defined by RECIST 1.1 OR evaluable disease with at least one site of disease that has not been previously radiated\n   2. Phase 2: At least one site of measurable disease on CT or MRI as defined by RECIST 1.1\n6. Meets organ function requirements as outlined below:\n\n   1. Liver:\n\n      Alanine aminotransferase (ALT) ≤ 2.5X upper limit of normal. For the purposes of this study the upper limit of normal for ALT is 45 U\u002FL. Aspartate aminotransferase (AST) ≤ 2.5X upper limit of normal. For the purposes of this study the upper limit of normal for AST is 50 U\u002FL. Total bilirubin ≤ 1.5X institutional upper limit of normal with the exception of patients with Gilbert's syndrome who must have bilirubin \\\u003C3X institutional upper limit of normal.\n   2. Renal:\n\n      Creatinine Calculated creatinine clearance (by the Schwartz equation for patients \\\u003C18 years of age and Cockroft-Gault formula (Appendix B) for patients ≥18 years of age) or radionuclide glomerular filtration rate (GFR) ≥ 50 mL\u002Fmin \u002Fm2 or a serum creatinine less than or equal to the age\u002Fgender valued below:\n\n      Age Maximum Serum Creatinine (mg\u002FdL) Male Female 10 to \\\u003C 13 years 1.2 1.2 13 to \\\u003C 16 years 1.5 1.4\n\n      ≥ 16 years 1.7 1.4\n   3. Bone marrow:\n\n      Absolute Neutrophil Count (ANC) ≥ 1,000\u002FµL (\\>one week since last dose of short acting medications (e.g. filgrastim) and \\> two weeks since last dose of long acting medications (e.g. peg-filgrastim)) Platelet Count (PLTs) ≥ 100,000\u002F µL (\\>two weeks since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days of screening laboratories) Patients with a history of bone marrow involvement are required to have bilateral bone marrow aspirates and biopsies at baseline. Subjects with bone marrow disease are eligible as long as they meet the hematologic requirements above and are not known to be refractory to red cell or platelet transfusions.\n   4. Muscle: Creatine phosphokinase (CPK) CTCAE 5 Grade ≤ 1,\n   5. Cardiac:\n\n   Creatine phosphokinase CTCAE 5 Grade ≤ l, Left ventricular ejection fraction (LVEF) or shortening fraction (SF) per institutional norm LVEF ≥50% OR SF ≥28%.\n7. Written, voluntary informed consent\n8. Fertile males and females of childbearing potential must agree to use an effective method of birth control from screening, through 7 months after last study drug administration for females and 4 months for males. Women of childbearing potential must have a negative pregnancy test during screening procedures. Effective methods of birth control include: double barrier method (condom, diaphragm), abstinence, an intrauterine device (IUD), levonorgestrol implants, medroxyprogesterone acetate injections, or oral contraception. For those subjects whose preferred and usual lifestyle employs abstinence, refraining from heterosexual intercourse must be practiced during the entire active phase of the trial.\n9. Patients ≥18 years must be willing to undergo tumor biopsy at study entry. Patients with Ewing sarcoma or DSRCT must be willing to undergo biopsy post-treatment. If biopsy is contraindicated, enrollment must be approved by study PI and archival tissue must be available.\n10. Time elapsed from previous therapy:\n\n    1. Must be ≥ 3 weeks for systemic myelosuppressive therapy\n    2. ≥ 2 weeks for local radiation therapy (small field), ≥ 150 days after thyrotropin binding inhibition (TBI), craniospinal external beam radiotherapy (XRT) or radiation to ≥50% of the pelvis\n    3. ≥ 2 weeks for major surgery\n    4. ≥ 2 weeks for monoclonal antibodies and oral kinase inhibitors.\n    5. ≥ 6 weeks for autologous stem cell transplant. 6 months for allogeneic stem cell transplant.\n    6. ≥ 6 weeks for any type of cellular therapy\n11. Patients must be recovered to baseline or Grade ≤1from the acute adverse effects of prior treatments, with the exception of alopecia and decreased deep tendon reflexes.\n\nExclusion Criteria:\n\n1. Prior therapy with trabectedin or lurbinectedin.\n2. Subjects with known brain metastases.\n3. Subjects with a known bleeding diathesis.\n4. Subjects who are pregnant or breastfeeding.\n5. Concurrent therapy:\n\n   1. Patients who are currently receiving an investigational drug or another anticancer agent\n   2. Patients receiving over the counter or herbal supplement with significant potential hepatotoxicity in the opinion of the investigator.\n   3. Patients receiving a medically necessary strong or moderate CYP3A4 inhibitor or inducer within 14 days prior to the first dose of study drug.\n6. Clinically significant, unrelated illness or uncontrolled infection which would, in the opinion of the treating physician, compromise the patient's ability to tolerate the investigational agents or be likely to interfere with the study procedures or results.\n7. Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.\n8. Patients with known active viral hepatitis (i.e. Hepatitis A, B, or C)\n9. Patients with Desmoplastic small round cell tumor (DSRCT) will be excluded from enrollment until at least 3 non-DSRCT patients have been enrolled without dose limiting toxicity.","10 Years",{"count":93,"type":19},63,[22,23],"The purpose of this study is to find out if a drug called lurbinectedin (the \"study drug\") is safe and effective at treating people with recurrent or relapsed solid tumors, including Ewing sarcoma.",[97,98,99,58],"Ewing Sarcoma","Desmoplastic Small Round Cell Tumor","Pediatric Cancer",[101,102,103,104,105,106,107],"Ewing Sarcoma-Friend Leukemia Integration 1 Transcription factor (ESW-FLI1)","Ewing Sarcoma Breakpoint Region 1-Friend Leukemia Integration 1 Transcription factor (EWSR1-FLI1)","Ewing Sarcoma Erythroblast Transformation Specific Related Gene (EWS-ERG)","Ewing Sarcoma Breakpoint Region 1 (EWRS1)","TATA-Box-Binding Protein Associated Factor 15 (TAF15)","Fused Tumors (FET)","Ewing Sarcoma-Wilms' Tumor Gene 1 (EWS-WT1)","2026-03-26",{"date":110,"type":74},"2026-03-31",{"date":112,"type":74},"2023-07-27",{"date":114,"type":19},"2028-07-30",{"name":116,"class":81},"Children's Hospital of Philadelphia",6,{"id":119,"slug":120,"hasResults":11,"nctId":121,"briefTitle":122,"officialTitle":123,"acronym":4,"eligibilityCriteria":124,"healthyVolunteers":11,"sex":15,"minAge":125,"maxAge":126,"enrollmentInfo":127,"targetDuration":4,"studyType":20,"phases":129,"briefSummary":130,"conditions":131,"keywords":137,"overallStatus":70,"whyStopped":4,"lastUpdateSubmitDate":146,"lastUpdatePostDateStruct":147,"startDateStruct":149,"completionDateStruct":151,"leadSponsor":153,"locationsCount":155},"100438877","phase-1-her2-chimeric-antigen-receptor-car-t-cells-in-combination-with-checkpoint-blockade-in-patients-with-advanced-sarcoma-100438877","NCT04995003","HER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma","Phase I Study of HER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma (HEROS 3.0)","Procurement Inclusion Criteria:\n\n* Diagnosis of a HER2-positive sarcoma. Immunohistochemistry (IHC) will be used to determine HER2 expression. Standard HER2 positive breast cancer density gradient tissue microarrays will be used as positive controls. HER2 expression will be graded for percent positive tumor cells (Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100%) and intensity of staining (Negative; 1+; 2+; and 3+). For the patient to meet eligibility, tumors are required to have at least ≥ grade 1 and ≥ 1+ intensity score for HER2 staining.\n* Age between 1 to 25 years\n* Karnofsky or Lansky performance score of ≥ 60\n* Informed consent explained to, understood by, and signed by patient\u002Fguardian. Patient or guardian given copy of informed consent.\n\nTreatment Inclusion Criteria:\n\n* Diagnosis of a HER2 positive sarcoma with active disease progression or recurrence after at least one prior systemic therapy\n* At least 4 weeks from and having recovered from acute toxic effects of all prior cytotoxic chemotherapy. Those receiving targeted (non-cytotoxic) drugs must be at least 7 days or 3 drug half-lives, whichever is greater, from last receipt of said drug and must have recovered from all acute toxic effects of that drug.\n* Normal cardiac left ventricular end diastolic function (LVEF) as measured by echocardiogram (normal per institutional limits)\n* Karnofsky or Lansky performance score of ≥60\n* Total bilirubin ≤1.5x upper limit of normal (ULN) for age AND direct bilirubin ≤ULN for age\n* AST\u002FALT ≤ 2.5x ULN\n* Serum creatinine ≤1.5x ULN for age\n* Hgb ≥ 7.0 g\u002FdL (transfusion allowed)\n* WBC \\> 2,000\u002Fµl\n* ANC \\>1,000\u002Ful\n* Platelets \\>75,000\u002Ful (not transfused)\n* Pulse oximetry of ≥ 90% on room air\n* Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the investigator. Non-childbearing potential is defined as pre-menarche, greater than 1-year post-menopausal, or surgically sterilized.\n* Available autologous transduced cytotoxic T lymphocytes with ≥ 15% expression of HER2 CAR and killing of HER2-positive targets ≥ 20% in cytotoxicity assay\n* Informed consent explained to, understood by, and signed by patient or guardian. Patient or guardian given copy of informed consent.\n\nProcurement Exclusion Criteria:\n\n* Known HIV positivity\n* Severe previous toxicity from cyclophosphamide including, but not limited to, decreased heart function, abnormal heart rhythms, severe allergic reaction, or grade 4 hemorrhagic cystitis\n* Severe previous toxicity from fludarabine including, but not limited to, neurotoxicity, coma, renal injury requiring dialysis, development of hemolytic anemia, or development of a secondary malignancy\n* Severe hypersensitivity (≥Grade 3) to pembrolizumab or nivolumab or any of their excipients\n* History of allergic reactions attributed to murine protein containing products, DMSO or dextran 40\n* Known, active cardiac disorder defined as left ventricular ejection fraction below the institution normal as determined by echocardiogram or New York Heart Association (NYHA) functional class III or IV or clinically significant cardiac arrhythmia.\n\nNote: A new echocardiogram or EKG is not required to make this determination.\n\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment\n* History of non-infectious pneumonitis that required steroids or current pneumonitis\n* Known history of active tuberculosis\n* Has undergone solid organ transplantation at any time\n* Has a diagnosis of immunodeficiency or is receiving any other form of immunosuppressive therapy aside from cytotoxic chemotherapy\n* Presence of bulky tumor at the primary or metastatic site\n* Has a history or current evidence of any condition, therapy, or laboratory or radiologic abnormality that is not in the best interest of the subject to participate, as determined by the treating investigator\n\nTreatment Exclusion Criteria:\n\n* Known HIV positivity\n* Intercurrent infection\n* Pregnant or lactating\n* History of hypersensitivity to murine protein-containing products, DMSO or dextran 40\n* Severe previous toxicity from cyclophosphamide including, but not limited to, decreased heart function, abnormal heart rhythms, severe allergic reaction, or grade 4 hemorrhagic cystitis\n* Severe previous toxicity from fludarabine including, but not limited to, neurotoxicity, coma, renal injury requiring dialysis, development of hemolytic anemia, or development of a secondary malignancy\n* Severe hypersensitivity (≥Grade 3) to pembrolizumab or nivolumab or any of their excipients\n* Cardiac disorder defined as left ventricular ejection fraction below the institution normal as determined by echocardiogram or New York Heart Association (NYHA) functional class III or IV or clinically significant cardiac arrhythmia\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n* History of non-infectious pneumonitis that required steroids or current pneumonitis\n* Known history of active tuberculosis\n* Has received a live virus vaccine within previous 30 days\n* Has undergone solid organ transplantation at any time\n* Has a diagnosis of immunodeficiency or is receiving any other form of immunosuppressive therapy\n* Presence of bulky tumor at the primary or metastatic site\n* Has received radiotherapy within 14 days of start of trial treatment with the exception that those who have received palliative radiation (≤ 10 days of radiotherapy) to non-central nervous system disease within 7 days are permitted. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.\n* Has a history or current evidence of any condition, therapy, or laboratory or radiologic abnormality that is not in the best interest of the subject to participate, as determined by the treating investigator","1 Year","25 Years",{"count":128,"type":19},25,[22],"The purpose of this study is to learn whether it is safe to give HER2-CAR T cells in combination with an immune checkpoint inhibitor drug (pembrolizumab or nivolumab), to learn what the side effects are, and to see whether this therapy might help patients with sarcoma.\n\nAnother goal of this study is to study the bacteria found in the stool of patients with sarcoma who are being treated with HER2 CAR T cells and immune checkpoint inhibitor drugs to see if the types of bacteria influence how well the treatment works.\n\nThe investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to see if they can put a new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new gene that the investigators will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor Receptor 2) that binds to sarcoma cells. In addition, it contains CD28, which stimulated T cells and make them last longer. After this new gene is put into the T cell, the T cell becomes known as a chimeric antigen receptor T cell or CAR T cell.\n\nIn another clinical study using these CAR T cells targeting HER2 as well as other studies using CAR T cells, investigators found that giving chemotherapy before the T cell infusion can improve the effect the T cells can have. Giving chemotherapy before a T cell infusion is called lymphodepletion since the chemotherapy is specifically chosen to decrease the number of lymphocytes in the body. Decreasing the number of the patient's lymphocytes first should allow the infused T cells to expand in the body, and potentially kill cancer cells more effectively.\n\nThe chemotherapy used for lymphodepletion is a combination of cyclophosphamide and fludarabine.\n\nAfter the patient receives the lymphodepletion chemotherapy and CAR T cells during treatment on the study, they will receive an antibody drug called an immune checkpoint inhibitor, pembrolizumab or nivolumab. Immune checkpoint inhibitors are drugs that remove the brakes on the immune system to allow it to act against cancer.",[132,133,134,135,97,47,136,58],"Sarcoma","HER-2 Protein Overexpression","Osteosarcoma","Rhabdomyosarcoma","Soft Tissue Sarcoma",[132,138,139,140,141,134,135,142,143,144,145],"Her-2 Positive Sarcoma","autologous T cells","HER2 positive recurrent or progressive sarcoma","HER2 CAR T cells","Ewing sarcoma","Synovial sarcoma","Soft tissue sarcoma","Undifferentiated sarcoma","2026-01-21",{"date":148,"type":74},"2026-01-22",{"date":150,"type":74},"2021-12-07",{"date":152,"type":19},"2043-06-30",{"name":154,"class":81},"Baylor College of Medicine",1]