Active clinical trials for "Glioblastoma"

The purpose of this study is to evaluate the safety and effectiveness in the treatment of recurrent glioblastoma with Cadonilimab combined with fractionated radiotherapy.

The study aims at investigating the cilium-related transcriptome in patients-derived glioblastoma stem cells and the potential impact of modulation of cilium players in vitro, in vivo and ex vivo in glioblastoma brain organoids. Moreover, drugs inhibiting cilia disassembly will be tested. Finally, the potential prognostic role of a cilium-related gene expression signature in glioblastoma will be assessed.

This is an observational study on GBM surgical samples to investigate if increasing doses of radiation therapy could improve the radiation response; and in particular the investigators will assess if there is a correlation between the number of the phosphorylated H2AX nuclear foci and the different dose level of radiation therapy.

Glioblastoma (GBM) is the most common primary brain cancer in adults. Surgery, chemoradiotherapy (temozolomide TMZ) and then adjuvant TMZ is the standard treatment. But, most patients relapse in a median time of 8-9 months; the median overall survival (OS) ranged from 15 to 18 months. Some frail patients received hypofractionated radiation and concomitant and adjuvant TMZ. For some, the radiation dose is not optimal. Moreover, recurrences develop mainly in the initial tumor site. These two reasons justify increasing the dose. To limit the movements of these fragile patients, the method consists of increasing the dose without increasing the number of sessions by using the Simultaneous Integrated Boost (SIB) which increases the dose in targeted volumes while the rest of the volume receives a minimum dose. A phase I trial showed the possibility of increasing the dose in SIB up to 80 Gy in a part of the GBM enhanced on MRI. FDOPA PET detects certain more aggressive tumor areas, areas likely to recur. Integrating them into the SIB seems appropriate. A phase II trial showed the interest of SIB guided by FDOPA PET in terms of progression-free survival but without impact on OS. This study differed from the one the investigators propose, because a dose and conventional fractionation, identical to that of the European Organization for Research and Treatment of Cancer/National Cancer Information Center (NCIC/EORTC) protocol were delivered, the gliomas were unmethylated MGMT, less likely to respond. Studies with SIB and hypofractionation are often retrospective and for others, hypofractionation was debatable and the dose increase was not based on PET capture but on MRI. However, a prospective phase II study, with SIB and hypofractionation, not integrating FDopa PET has demonstrated the relevance of SIB. In this project, the investigators propose to use the integrated boost technique (SIB) guided by PET FDOPA to increase the radiation dose in GBM, in patients either fragile and partially operated, or only biopsied and for whom the prognosis is the most pejorative.

This is a Phase 1 study of recurrent glioblastoma locoregional adoptive therapy with autologous peripheral blood T cells lentivirally transduced to express a dual-target, truncated IL7Ra modified chimeric antigen receptor (CAR), delivered by Ommaya reservoir, a pre-indwelled catheter in the tumor resection cavity. Patients with recurrent glioblastoma will have surgical treatment and pathological test for target expression at their home institution or at Beijing Tiantan Hospital. If the tumor is target positive and the patient meets all other eligibility criteria, and meets none of the exclusion criteria, will have Ommaya reservoir implantation, and a subsequent Peripheral Blood Mononuclear Cells (PBMCs) collection. T cells will then be isolated from the PBMC sample and then be bioengineered in to a 4th generation CAR-T cell, Tris-CAR-T cells. Recipients with Ommaya reservoir implanted will be assigned to three courses. The first 2 patients will be assigned to low dose group, and will have one dose of autologous Tris-CAR-T cells delivery via Ommaya reservoir. The second 2 patients will be assigned to high dose group, and will have one dose of autologous Tris-CAR-T cells delivery via Ommaya reservoir. The last 4 patients will be assigned to multidose group, and will receive a weekly dose of autologous Tris-CAR-T cells for maximum 8 weeks. All patients will undergo studies including MRI to evaluate the effect of the CAR-T cells, physical examination and cerebrospinal fluid cytokine assays to evaluate side effects. All patients will undergo a long-term follow-up. The hypothesis is that an adequate amount of Tris-CAR-T cells can be manufactured to complete all the three courses. The other hypothesis is that Tris-CAR-T cells can safely and effectively be administered through Ommaya reservoir to allow the CAR-T cells to directly interact with the tumor cells for each patient enrolled on the study. The primary aim of the study will be to evaluate the safety of Tris-CAR-T administering. Secondary aims of the study will include to evaluate CAR-T cell distribution within cerebrospinal fluid and peripheral blood, tumor progress post CAR-T cell infusion, and, if tissues samples from multiple time points are available, also evaluate the degree of target expression, biological characteristics of samples at diagnosis versus at recurrence or progression.

To learn if the Exablate Model 4000 Type 2 ("Exablate System") with the DEFINITY® ultrasound contrast agent can temporarily disrupt the blood brain barrier in patients with recurrent (has grown back) glioblastoma who are scheduled to receive pembrolizumab.

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.

This is to study if neoadjuvant atezolizumab therapy is beneficial for patients with recurrent glioblastoma and a low mutational burden.

The purpose of this study is to better define longitudinal genomic alterations in patients with glioblastoma (GBM), and to determine if plasma circulating tumor DNA (ctDNA) or cell free DNA (cfDNA) is associated with disease recurrence, survival, tumor characteristics, and/or peripheral immunosuppression.

Temozolomide provided significant and clinically meaningful benefit in MGMT gene promoter methylation glioblastoma. However, in unmethylated patients, the effect of Temozolomide is limited. The aim of this study is to compare the effect of Etoposide plus Cisplatin and Temozolomide in patients with MGMT gene promoter unmethylation glioblastoma.