Glioblastoma clinical trials at University of California Health

Glioblastoma (GBM) is the most common malignant brain tumor among adults. As the diagnosis is generally considered terminal, patients with GBM often suffer from anxiety and other comorbid conditions, including depression, pain, and sleep disturbance, all of which significantly impact their quality of life. Previous studies have demonstrated the potential of cannabinoids, particularly cannabidiol (CBD), to improve the aforementioned symptoms without conferring significant risks or side effects. Further, recent in-vitro and in-vivo work suggests potential cytotoxic and anti-tumor effects of CBD and other cannabinoids. This study includes a double-blind, placebo-controlled, 8-week randomized clinical trial assessing the impact of a custom formulated, full-spectrum, hemp-derived ultra-high CBD product on measures of anxiety, pain, and quality of life in newly-diagnosed GBM patients undergoing standard of care (SOC) treatment; the impact of this product vs. placebo on tumor progression will also be assessed. The proposed clinical trial will provide important information that does not currently exist regarding the potential efficacy of a novel full-spectrum, ultra-high CBD product to address clinical symptoms in patients with GBM.

This is a Phase 2, randomized two-armed, multi-site study of 170 patients with newly diagnosed glioblastoma multiforme. Patients will be randomized 1:1 to receive Keto Diet, or Standard Anti-Cancer Diet. All patients will receive standard of care treatment for their glioblastoma. The Keto Diet intervention will be for an 18-week period and conducted by trained research dietitians. Daily ketone and glucose levels will be recorded to monitor Keto Diet adherence. This two-armed randomized multi-site study aims to provide evidence to support the hypothesis that a Keto Diet vs. Standard Anti-Cancer Diet improves overall survival in newly diagnosed glioblastoma multiforme patients who receive standard of care treatment.

This is a phase 0/I exploratory study. Patients at first or second recurrence of glioblastoma will be enrolled. The study will be divided into two cohorts: Cohort A (safety cohort) and Cohort B (surgical patient cohort). Cohort A: Eligible patients will be sequentially enrolled to receive intravenous domvanalimab combined with zimberelimab (N=6). Domvanalimab will be given at a dose of 10 mg/kg and zimberelimab will be given at a dose of 240 mg (flat). The dosing was determined in a separate study in solid tumors; this cohort will confirm the safety of the dosing schedule in patients with brain tumors. Cohort B: Expansion surgical cohort. The purpose of cohort B is to provide an additional safety evaluation of domvanalimab + zimberelimab as well as tissue and blood for exploratory ancillary studies investigating the effects of domvanalimab + zimberelimab in the tumor and tumor microenvironment. A total of 46 patients will be enrolled in this cohort.

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.

This phase I/Ib trial tests the side effects, best dose, tolerability, and effectiveness of RMC-5552 in treating patients with glioblastoma that has come back (recurrent). RMC-5552 is a type of medicine called an mechanistic target of rapamycin (mTOR) inhibitor. These types of drugs prevent the formation of a specific group of proteins called mTOR. This protein controls cancer cell growth, and the study doctors believe stopping mTOR from forming may help to kill tumor cells.

There is no consensus on the optimal treatment of patients with high-grade glioma, especially when patients have limited functioning performance at presentation (KPS ≤70). Therefore, there are varied practice patterns around pursuing biopsy, resection, or palliation (best supportive care). This study aims to characterize the impact of palliative care versus biopsy versus resection on survival and quality of life in these patients. Also, it will aim to determine if there is a subset of patients that benefit the most from resection or biopsy, for which outcome, and how they could be identified preoperatively. This study is an international, multicenter, prospective, 3-arm cohort study of observational nature. Consecutive HGG patients will be treated with palliative care, biopsy, or resection at a 1:3:3 ratio. Primary endpoints are: 1) overall survival, and 2) quality of life at 6 weeks, 3 months and 6 months after initial presentation based on the EQ-5D, EORTC QLQ C30 and EORTC BN 20 questionnaires. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

Previous evidence has indicated that resection for recurrent glioblastoma might benefit the prognosis of these patients in terms of overall survival. However, the demonstrated safety profile of this approach is contradictory in the literature and the specific benefits in distinct clinical and molecular patient subgroups remains ill-defined. The aim of this study, therefore, is to compare the effects of resection and best oncological treatment for recurrent glioblastoma as a whole and in clinically important subgroups. This study is an international, multicenter, prospective observational cohort study. Recurrent glioblastoma patients will undergo tumor resection or best oncological treatment at a 1:1 ratio as decided by the tumor board. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks after surgery and 2) overall survival. Secondary endpoints are: 1) progression-free survival (PFS), 2) NIHSS deterioration at 3 months and 6 months after surgery, 3) health-related quality of life (HRQoL) at 6 weeks, 3 months, and 6 months after surgery, and 4) frequency and severity of Serious Adverse Events (SAEs) in each arm. Estimated total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year. The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

There are no guidelines or prospective studies defining the optimal surgical treatment for gliomas of older patients (≥70 years) or those with limited functioning performance at presentation (KPS ≤70). Therefore, the decision between resection and biopsy is varied, amongst neurosurgeons internationally and at times even within an instiutition. This study aims to compare the effects of maximal tumor resection versus tissue biopsy on survival, functional, neurological, and quality of life outcomes in these patient subgroups. Furthermore, it evaluates which modality would maximize the potential to undergo adjuvant treatment. This study is an international, multicenter, prospective, 2-arm cohort study of observational nature. Consecutive HGG patients will be treated with resection or biopsy at a 3:1 ratio. Primary endpoints are: 1) overall survival (OS) and 2) proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy. Secondary endpoints are 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months and 6 months after surgery 2) progression-free survival (PFS); 3) quality of life at 6 weeks, 3 months and 6 months after surgery and 4) frequency and severity of Serious Adverse Events (SAEs). Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

A greater extent of resection of the contrast-enhancing (CE) tumor part has been associated with improved outcomes in high-grade glioma patients. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in HGG patients in terms of survival, functional, neurological, cognitive, and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively. This study is an international, multicenter, prospective, 2-arm cohort study of observational nature. Consecutive HGG patients will be operated with supramaximal resection or maximal resection at a 1:3 ratio. Primary endpoints are: 1) overall survival and 2) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months, and 6 months postoperatively. Secondary endpoints are 1) residual CE and NCE tumor volume on postoperative T1-contrast and FLAIR MRI scans 2) progression-free survival; 3) onco-functional outcome, and 4) quality of life at 6 weeks, 3 months, and 6 months postoperatively. The study will be carried out by the centers affiliated with the European and North American Consortium and Registry for Intraoperative Mapping (ENCRAM).