Glioblastoma Clinical Trials

Current standard of care therapy and all FDA approved adjuvant therapy for glioblastoma continue to provide less than 12 months of progression free survival (PFS) and less than 24 months of overall survival (OS). There is an extreme need for any novel therapy against glioblastoma that increases progression free survival and overall survival in patients diagnosed with this invasive form of cancer. A significant reason for such a poor prognosis is the infiltrative nature of this tumor in non-enhancing regions (NE) beyond the central contrast-enhancing (CE) portion of tumor, which is difficult to visualize and treat with surgical, medical, or radiotherapeutic means. Since tumor cells exhibit abnormal metabolic behavior leading to extracellular acidification, we theorize a newly developed pH-sensitive MRI technique called amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) may identify infiltrating NE tumor beyond what is clear on standard MRI with gadolinium contrast. This phase I safety study will use use intraoperative CEST-EPI guided resections in glioblastoma at increasing distances from areas of CE tumor to test whether this technique is safe and can remove additional areas of infiltrative NE tumor. The primary objective of this study is to assess the safety of pH-sensitive amine CEST-EPI guided resections for glioblastoma.The secondary objectives of this study include: 1. A preliminary efficacy analysis of CEST-EPI guided resections in extending progression free and overall survival. 2. To confirm that resected tissue obtained from pH-sensitive amine CEST-EPI guided resections contain infiltrating NE tumor. The primary endpoint for this study will be safety of resecting "CEST positive", acidic regions within T2 hyperintense regions of glioblastoma thought to contain active NE tumor at increasing distances from contrast enhancing tumor with development of a recommended maximal tolerated resection. 1. At the maximal tolerated resection, a preliminary efficacy study with endpoints of progression free survival (as defined by RANO Resect 2.0) 1 and overall survival. 2. Quantitation of infilitrating tumor burden on CEST-EPI resected tissue using immunohistochemical staining. 12 patients up to 24 patients based on resection limiting toxicities with potential expansion of up to 16 patients at the maximum tolerated resection. Inclusion Criteria: 1. Must be able to provide written informed consent 2. Male or female \> 18 years of age 3. Karnofsky Performance Scale (KPS) \> 70 (indicating good performance status). 4. Individuals with suspected, newly diagnosed or recurrent IDH wild type WHO IV glioblastoma (intraxial, expansile contrast-enhancing mass without evidence of metastatic disease. This will be reviewed by UCLA neuroradiology to only include patients with high likelihood of GBM) Exclusion Criteria: 1. Pediatric patients 2. Diagnostic uncertainty (reviewed by UCLA neuroradiology history extracranial malignancy or autoimmune disease) 3. Medical conditions that make patients a poor candidate for anesthesia and/or surgery (decision for surgery will follow standard pre-operative clearance guidelines and will not differ for this specific study from standard of care treatment plan) 4. Involvement of eloquent areas (as defined by MRI signal clearly involving areas that would lead to a qualifying neurologic deficit as defined in surgical limiting toxicity - this will specifically include: 1) primary motor cortex, 2) primary sensory cortex, 3) sensorimotor fibers as defined on pre-operative diffusion tensor imaging, 4) primary language areas (Broca, Wernicke), 5) arcuate fasiculus as defined on pre-operative diffusion tensor imaging Pre-operative: Standard of care pre-operative MRI including perfusion and pH-weighted amine CEST-EPI (which will add up to 15 minutes of scan time) for a single pre-operative exam prior to surgery. Surgery: 1 day (subjects to be admitted to the hospital) Follow-up: inpatient stay (1-3 days), 2 week clinical assessment (outpatient post-op clinic visit). MRI and clinical assessment at 4 weeks (end of resection limited toxicity window). Following this, there will be standard of care follow up with MRI and clinical assessment starting at 8 weeks +/- 4 weeks (per RANO 2.0). 1 Total study duration for recruitment, enrollment, and study completion of all subjects is up to 2 years. Single-arm, surgical resection escalation safety trial with a preliminary efficacy study at the maximal tolerated resection This safety evaluation will mimic a phase 1 dose escalation safety study using a rule based approach on based on a i3+3 design.2 Using standard of care resection of contrast enhancement as the baseline, we will begin with 3 subjects with maximal resection + "CEST positive" areas 0.7 cm from the contrast enhancing boundary within areas of T2 hyperintensity. If there is not \> 1 pre-determined resection limiting toxicity (RLT, defined below) in this cohort, the r Read Less

A Dose Finding Study of \[177Lu\]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination with Standard of Care and in Recurrent Glioblastoma as a Single Agent Read Less

The purpose of this study is to test WSD0628 in combination with radiation therapy for recurrent brain tumors. Read Less

This research study is studying a new type of vaccine as a possible treatment for patients with glioblastoma. This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the intervention to use for further studies. "Investigational" means that the intervention is being studied and that research doctors are trying to find more about it. It also means that the FDA (U.S. Food and Drug Administration) has not approved the Personalized NeoAntigen Cancer Vaccine for any use in patients, including people with glioblastoma. The purpose of the initial study cohort (Cohort 1) is to determine if it is possible to make and administer safely a vaccine against glioblastoma by using information gained from specific characteristics of the participants tumor. It is known that glioblastomas have mutations (changes in genetic material) that are specific to an individual patient's tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the body fight any tumor cells that could cause the glioblastoma to come back in the future. Three additional cohorts (1a, 1b, \& 1c) were added to the study following completion of accrual to the original study cohort (cohort 1). Each new cohort receives NeoVax and radiation therapy as administered to cohort 1 and will also receive pembrolizumab: cohort 1a patients will start pembrolizumab w/in 2 weeks after start of RT, and continue every 3 weeks for up to 2 years; cohort 1b patients will start pembrolizumab 2-4 weeks after completion of NeoVax priming, and continue every 3 weeks for up to 2 years; cohort 1c patients will receive a single dose of pembrolizumab administered within 2 weeks after start of RT, re-start 2-4 weeks after completion of NeoVax priming, and continue every 3 weeks for up to 2 years. The rationale for adding these new cohorts is: 1) to assess the safety and feasibility of NeoVax when administered with pembrolizumab; and 2) to determine if the timing of anti-PD-1 administration impacts the immunogenicity of NeoVax. An additional sub-study cohort (1d) is being added for patients whose tumor is MGMT-methylated. Cohort 1d will enroll patients with tumors for which the MGMT status is methylated or partially methylated; patients on cohort 1d will receive standard daily temozolomide during radiation and as adjuvant therapy for up to six cycles following completion of radiation therapy. The rationale for adding cohort 1d is to determine the safety and feasibility of NeoVax when administered with pembrolizumab and temozolomide. Read Less

This is a phase 2 open-label study to evaluate the safety and efficacy of N-803 and PD-L1 t-haNK when combined with Bevacizumab in subjects with recurrent or progressive GBM. Participants will receive N-803 subcutaneously (SC), PD-L1 t-haNK intravenously (IV), and Bevacizumab IV combination therapy. Treatment for all enrolled participants will consist of repeated cycles of 28 days for a maximum treatment period of 76 weeks (19 cycles). Treatment will be administered on days 1 and day 15 of each cycle. Treatment will be discontinued if the participant reports unacceptable toxicity (not corrected with dose reduction), withdraws consent, if the Investigator feels it is no longer in the participant's best interest to continue treatment, or the participant has confirmed progressive disease by iRANO, unless the participant is potentially deriving benefit per Investigator's assessment. Participants will be followed for collection of survival status every 12 weeks (± 2 weeks) for the first 2 years, then yearly thereafter. Read Less

The primary objective of this Phase 1, open-label, dose-escalation, and exploratory study is to evaluate the safety and tolerability profile (establish the maximum-tolerated dose) and evaluate the occurrence of dose-limiting toxicities (DLTs) following single weekly or multiple-day weekly dose regimens of single-agent, oral ONC206 in patients with recurrent, primary central nervous system (CNS) neoplasms. Read Less

This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BGB-290 and temozolomide may work better in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma. Read Less

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose and the recommended Phase 2 dose of ivonescimab that can be given to patients who have recurrent glioblastoma. The goal of Phase 2 of this clinical research study is to learn if the recommended Phase 2 dose of ivonescimab found in Phase 1 can help to control the disease. Read Less

This phase I/Ib trial tests the safety, side effects, and best dose of mycophenolate mofetil in combination with temozolomide and/or radiation therapy (standard of care) in treating patients with glioblastoma. Mycophenolate mofetil is an immunosuppressant drug that is typically used to prevent organ rejection in transplant recipients. However, mycophenolate mofetil may also help chemotherapy with temozolomide work better by making tumor cells more sensitive to the drug. The purpose of this trial is to determine if mycophenolate mofetil combined with temozolomide can stop glioblastoma. Read Less

This is an open-label phase 1 study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy of autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL3Ra2 (referred to as "CART-EGFR-IL13Ra2 cells"). Patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma who have undergone maximal safe surgical resection will be approached for initial study participation. A two-step screening/eligibility process will be utilized. Following informed consent, subjects who meet Step #1 Eligibility Criteria will remain on study and complete a course of radiotherapy (60 Gy) without temozolomide as per their routine cancer care. If there is no overt evidence of disease recurrence/progression following radiotherapy, additional screening tests/procedures will be performed. Subjects who then meet Step #2 Eligibility Criteria will undergo apheresis collection to initiate cell product manufacturing and surgical placement of a CSF-Ventricular Reservoir to allow for intracerebroventricular injection of the CART-EGFR-IL13Ra2 cells. All subjects will receive a single fixed dose of CART-EGFR-IL13Ra2 cells on Day 0 via intracerebroventricular delivery. Read Less

This pilot study will assess the safety and feasibility of using an implantable microdevice to measure local intratumor response to chemotherapy and other clinically relevant drugs in malignant brain tumors. * The device involved in this study is called a microdevice. * The drugs used in this study will only include drugs already used systemically for the treatment of gliomas. Read Less

MicroRNAs (miRNA) are molecular biomarkers that post-transcriptionally control target genes. Deregulated miRNA expression has been observed in diverse cancers. In high grade gliomas, known as glioblastomas, the investigators have identified an oncogenic miRNA, miRNA-10b (mir-10b) that is expressed at higher levels in glioblastomas than in normal brain tissue. This study tests the hypothesis that in primary glioma samples mir-10b expression patterns will serve as a prognostic and diagnostic marker. This study will also characterize the phenotypic and genotypic diversity of glioma subclasses. Furthermore, considering the critical function of anti-mir-10b in blocking established glioblastoma growth, the investigators will test in vitro the sensitivity of individual primary tumors to anti-mir-10b treatment. Tumor, blood and cerebrospinal fluid samples will be obtained from patients diagnosed with gliomas over a period of two years. These samples will be examined for mir-10b expression levels. Patient survival, as well as tumor grade and genotypic variations will be correlated to mir-10b expression levels. Read Less