Glioblastoma

This study is assessing the safety and tolerability of 5-ALA- mediated Porphyrin Metabolite Activation (PoMA) with LIDU ultrasound, in patients who have just been diagnosed with bihemispheric (in both sides of the brain) glioblastoma, sometimes called butterfly glioblastoma, before they complete their standard of care chemotherapy and radiation and after their standard of care chemotherapy and radiation while they are receviing their standard of care adjuvant chemotherapy.

This clinical trial tests the impact of tear fluid in detecting tumor-associated extracellular vesicles (TEVs) in patients with glioblastoma. Brain tumors release small particles, called TEVs, that may provide information about the tumor, including how it responds to treatment. These particles can be found in cerebrospinal fluid (CSF), which is the fluid that surrounds the brain and spinal cord. Collecting CSF can be difficult and expensive, especially if samples are needed frequently to track these particles over time. Tear fluid is easier to collect than spinal fluid. If tears are found to contain similar tumor-related particles, changes in the tumor may be tracked by studying the particles found in tear fluid.

Better treatments are needed for high-grade gliomas (HGG), and new ways of treating this disease should be tested. The investigators want to see if giving medicine before radiation works well. After radiation, MRI scans can be harder to understand because radiation changes how the brain looks on the scan. If new medicines are given before radiation, the scans are easier to read. First, the investigators need to find out if giving chemotherapy early works using a drug we already know can treat gliomas. The investigators will start with temozolomide, which is the only chemotherapy approved by the FDA for HGG. If this approach is successful, the investigators can then test new drugs using this screening method.

To date, very little data exists on gliomas in the Réunion population, in terms of epidemiology, socio-cultural aspects, clinical or biological factors, and care pathways. However, the Réunion population is multicultural and highly cosmopolitan, experiencing rapid aging, and its socio-economic indicators are among the most pessimistic of all French departments. Furthermore, the healthcare services available on the island are less comprehensive than those in metropolitan France (Insee 2018). Finally, the management of patients with gliomas, particularly high-grade gliomas, remains very complex, with significant medical and social challenges (supportive care, end-of-life care, etc.). Healthcare professionals agree that these specialized facilities are insufficient to meet the care needs in Réunion (post-acute care, palliative care units, supportive care, etc.). GlioRun is a retrospective and prospective mixed-methods cohort study, combining epidemiological and socio-anthropological approaches, which aims to produce data to improve care and the experiences of patients and their relatives on Reunion Island, and reduce the number of medical evacuations to mainland France.

This is a Phase 3 prospective, randomized, superiority, open-label, multi-site study. The overview of this study is as follows: * A Screening/Baseline Period of 21 days. During this time, patients will be randomized into a 1:2 allocation of Arm A:Arm B. * A Perioperative/Operative Phase where patients will undergo tumor resection (Arm A) or tumor resection plus GammaTile implantation (Arm B). * An EBRT Prior to Start Period. This occurs within 10 business days prior to EBRT and Concurrent TMZ Phase. * An EBRT and Concurrent TMZ Phase, which will begin 30 ±10 days post-surgery. EBRT (30 fractions) and TMZ will be administered up to 5 days a week for 6 weeks in Arm A, and EBRT (20 fractions) and TMZ will be administered for up to 5 days a week for 4 weeks in Arm B. TMZ will be administered at a dose of 75 mg/m2/day orally for each Arm. * An Adjuvant TMZ Phase, which begins 28 ±7 days following the EBRT and Concurrent TMZ Phase, and is comprised of six 28-day cycles. TMZ (150-200 mg/m2/day orally) will be administered for the first 5 days of each 28-day cycle for each Arm. Tumor treating fields are allowed but are not mandated during this phase. Up to 6 additional cycles (for a total of 12) can be completed at the discretion of the Investigator. * An Early Discontinuation/Follow-Up Phase will occur 28 ±7 days after completion of Cycle 6 of the Adjuvant TMZ Phase, regardless of the total number of cycles completed or any delays in cycle start. If fewer than six cycles are completed, the first follow-up assessment will occur 28 ±7 days after the last administered dose of adjuvant TMZ. If patient has a qualifying event requiring entrance to Early Discontinuation Phase, the first follow-up assessment will occur as soon as feasible, but within 28 days. For any unscheduled visits, data collected should be documented in the case report form (CRF) and must include, but are not limited to, safety evaluations, survival status, and disease status.

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.

The goal of this clinical trial is to: 1) evaluate the safety, tolerability, and recommended dose of dexbrompheniramine when combined with metronomic temozolomide for adults with recurrent high-grade glioma who have been previously treated with standard of care chemoradiation therapy and 2) determine the efficacy of the combination therapy in adults with glioblastoma who progressed during the first six cycles of adjuvant standard dose temozolomide. The main questions it aims to answer are: * What medical problems to participants have when taking dexbrompheniramine together with temozolomide? * What is the correct dose of dexbrompheniramine to use when evaluating the safety and efficacy of the combination therapy? * Is the combination therapy more effective at delaying disease progression compared to temozolomide alone? Participants will take dexbrompheniramine and temozolomide every day at night.

This phase II trial studies whether providing cancer treatment in the home is preferred over the traditional clinic setting and if it improves treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas. Typically, drug-related cancer care is provided at a medical center which causes patients to have to spend considerable time away from their family, friends, and familiar surroundings. This may add to the physical, emotional, social, and financial burden for patients and their families during this difficult time in their lives. The Cancer Connected Access and Remote Expertise (CARE) Beyond Walls (CCBW) program uses a specialized care team trained to provide cancer treatment in the patient's home setting. It is designed to support remote connection between the home health team and providers and Mayo clinic. This may be preferred over the traditional clinic setting which may improve treatment satisfaction in cancer patients living in the Florida Panhandle and surrounding areas.

The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Half the people in the study will be assigned to take the study drug ruxolitinib in addition to the standard of care temozolomide and radiation therapy and the other half will be assigned to the standard of care temozolomide and radiation therapy only. This assignment will be randomized in a 1-to-1 ratio, like the flip of a coin.

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM. All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (\*).

The objectives of this phase I first-in-human trial are to evaluate safety, feasibility, and preliminary efficacy of an individualized Bvax vaccine in addition to standard of care chemoradiation in patients with newly diagnosed glioblastoma.

This is a phase 1 study evaluating the safety and feasibility of laser interstitial thermal therapy (LITT) followed by lomustine (CCNU) for recurrent glioblastoma in adults. The primary aim is to evaluate the safety of the combination of LITT plus lomustine based on the assessment of treatment-related adverse events and the feasibility of completing LITT + lomustine in the proposed timeframe. The secondary aim is to assess overall survival for up to 2 years after the first dose of lomustine.

The immune system plays a critical role in cancer progression and antitumor responses. Glioblastoma is an aggressive and incurable brain tumor characterized by a highly immunosuppressive microenvironment. Over the past two decades, photodynamic therapy (PDT) has been evaluated as an adjunct to fluorescent-guided resection (FGR) and chemoradiotherapy according to the STUPP protocol, for resectable glioblastomas. In addition to demonstrating the feasibility of such a procedure, two previous clinical trials (INDYGO, NCT03048240; DOSINDYGO, NCT04391062) revealed/highlighted significant systemic immune changes following treatment, including modifications in peripheral blood mononuclear cells (PBMCs) activation and cytokine secretion profiles. However, the specific contribution of PDT remains uncertain due to the combined effects of, on the one hand, PDT and, on the other hand, FGR and chemoradiotherapy. This study aims to evaluate immune parameters in a control population undergoing FGR and chemoradiotherapy only (i.e., without PDT). The objective is to distinguish the immunological impact of PDT from that of FGR and chemoradiotherapy. The results will provide a better understanding of the systemic immune modulation induced by PDT in glioblastoma.

This is a Phase 0 investigational study to assess the central nervous system penetration and tumoral concentration of gallium in patients with recurrent glioblastoma administered with preoperative gallium maltolate.

This is a phase 2, open-label clinical trial determining feasibility, safety, and tolerability of GammaTile® in elderly or frail subjects with newly diagnosed or recurrent malignant gliomas.

REMIND is a single-center feasibility study testing maintenance radiotherapy in adult patients with newly diagnosed glioblastoma. Participants will be consented before starting standard-of-care concurrent temozolomide and radiotherapy. After enrollment, participants will enter an observational lead-in phase while receiving standard-of-care therapy off study. Approximately 4 weeks after temozolomide, participants will receive one study-specific 2 Gy fraction of maintenance radiotherapy directed at the post-operative cavity and areas of prior enhancing disease. The study will evaluate the safety and feasibility of delivering maintenance radiotherapy. Blood samples will also be collected before and after maintenance radiotherapy to descriptively compare myeloid-derived suppressor cell frequency.

The goal of this clinical trial is to see if the combination of valproic acid, irinotecan, and simvastatin causes these tumors to stabilize or shrink, which is a sign that these combinations are effective against tumors in patients with recurrent glioblastoma and adults with recurrent IDH-mutated gliomas

This investigator-initiated, multicenter clinical trial will evaluate the safety and preliminary effectiveness of adding entacapone to bevacizumab in adults with isocitrate dehydrogenase (IDH)-wildtype glioblastoma at first recurrence after standard first-line treatment. Participants must not have previously received bevacizumab. A multidisciplinary neuro-oncology team must determine that repeat tumor resection is not appropriate, or the patient must decline repeat surgery after being informed of its potential benefits and risks. The study has two stages. In the first stage, 6 participants who can be evaluated for dose-limiting toxicity will receive open-label entacapone 400 mg by mouth three times daily plus bevacizumab. Enrollment will occur in two cohorts of 3, with safety review by an independent data and safety monitoring board. Up to 3 participants who cannot complete the 28-day toxicity evaluation for reasons unrelated to toxicity may be replaced. If the combination has acceptable safety and the required approvals are obtained, 90 new participants will enter the second stage and be randomly assigned in a 1:1 ratio to entacapone or matching placebo. Both groups will receive bevacizumab. The primary endpoint of the randomized stage is progression-free survival assessed by blinded independent central review. The study plans to obtain data from 96 evaluable participants, with no more than 99 participants receiving study treatment.

This phase Ib trial tests the safety and side effects of ERAS-801 in treating patients with isocitrate dehydrogenase (IDH) wildtype, epidermal growth factor receptor (EGFR) amplified or mutated grade IV glioblastoma or gliosarcoma that can be removed by surgery (resectable) and that is growing, spreading, or getting worse (progressive), that has come back after a period of improvement (recurrent) or that is newly diagnosed in an elderly patient. Glioblastoma is the most common brain cancer in adults and survival rates remain poor despite treatment including surgery, radiation and chemotherapy. EGFR is a protein found on the surface of some cells, to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of tumor cells, so these cells may divide excessively in the presence of epidermal growth factor. ERAS-801, an EGFR inhibitor that can penetrate the central nervous system, binds to the tumor cells that express EGFR and may help shrink or slow the growth of the tumor cells.

Advanced technology of ex vivo drug profiling referred to as pharmacoscopy may allow to identify novel drugs for the treatment of glioblastoma and other refractory brain tumors at an individual patient level. This personalized therapeutic approach was developed and validated in pre-clinical glioma models. With the current research proposal, we seek to establish feasibility for a clinical interventional trial for patients with refractory primary brain tumors that is based on pharmacoscopy-guided selection of treatment. The study is supported by an unrestricted grant from Anti Cancer Fund.

This is an open label, intra-patient dose escalation, to evaluate ADI-PEG 20, in combination with Temozolomide (TMZ) and radiation therapy (RT) in children, adolescents and young adult patients with newly diagnosed high grade glioma (HGG).

Neurovascular uncoupling (NVU) represents a major source of potential bias for the identification of eloquent brain regions through activation procedures in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Same region shows proper pattern in glucose metabolism in victiny of brain lesions, investigated with positron emitted tomography with radiolabeled glucose (PET-FDG) This research project aims at investigating the mechanisms of NVU by using a multimodal noninvasive imaging approach in neurosurgical patients.

In Australia, glioblastoma (GBM) has a higher annual fatality rate than a variety of other cancers, such as melanoma, bladder, and kidney tumors. While the 5-year survival rate for other cancers, such as breast and prostate cancer, has increased, there have been no notable advancements in GBM during the past ten years, and the incidence and mortality patterns have barely changed between 1982 and 2011. In particular, GBM poses a challenging therapeutic dilemma for patients and physicians due to its aggressive biology and resistance to available treatments. Recent studies showed that cytomegalovirus (CMV) is expressed in GBM tumors, making it a good target for immunotherapy trials. This phase I trial aims to determine the safety and tolerability of the PEP-CMV vaccine in patients with newly diagnosed MGMT-unmethylated GBM in combination with one cycle of adjuvant temozolomide.

Glioblastoma (GBM), WHO grade IV glioma, represents the majority of adult malignant primary brain tumors, with an incidence of 2-3 per 100,000 person-years. The survival for GBM has increased in the last decade but is still low with a median survival of 15-18 months. Recurrence after initial standard therapy, radiation therapy and chemotherapy with temozolomide, few options are available. Even with further therapy, median progression free survival at 6 months after first relapse (PFS-6) is only 15%. Similarly, anaplastic astrocytoma and anaplastic oligodendroglioma, grade III gliomas, once recurrent after radiation therapy and first-line chemotherapy, have identical therapeutic options and poor outcomes with PFS-6 of 31%. Temozolomide (TMZ) has a favorable side effect profile and is available orally, however, cytotoxicity occurs. Metronomic temozolomide at low doses on a continuous schedule, have demonstrated better survival in studies. This study will determine the recommended dose and the side effects of PCI-24781/Abexinostat with metronomic temozolomide.

The researchers are doing this study to find out whether the drugs ABBV-637 and ABBV-155 are safe treatments that cause few or mild side effects when given alone or in combination with ERAS-801 in people with recurrent GBM.