View clinical trials related to Glioblastoma.
Filter by: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.
Glioblastoma, the most prevalent malignant tumor in the central nervous system, is characterized by high invasiveness and a propensity to recur, contributing to a relatively elevated mortality rate. Patients diagnosed with high-grade glioblastomas typically experience a median survival period of less than 14 months. Presently, the standard treatment for glioblastoma involves surgical resection combined with postoperative radiotherapy and chemotherapy, with postoperative chemotherapy playing a pivotal role in enhancing patient prognosis. Temozolomide (TMZ), a cutting-edge oral alkylating agent known for its advantageous properties, including easy traversal of the blood-brain barrier, induces DNA alkylation in tumor cells, fostering apoptosis. Currently, it serves as a frontline medication for postoperative chemotherapy in glioblastoma. However, clinical resistance to TMZ chemotherapy significantly hampers its efficacy in later stages. We have recently discovered and validated that 5-aminoimidazole-4-carboxamide (AICA), derived from TMZ, can transform into 5-aminoimidazole-4-carboxamide ribonucleotide-5-phosphate (AICAR) in GBM cells. Hypoxanthine phosphoribosyltransferase 1 (HPRT1) has been identified as the catalyst for the AICA reaction, generating AICAR. AICAR acts as an endogenous activator of AMP-activated protein kinase (AMPK), fostering chemoresistance in glioblastoma through the activation of the AMPK signaling pathway. 6-mercaptopurine (6-MP) competes effectively to inhibit HPRT1 activity, thereby impeding TMZ-induced AMPK activation and significantly heightening glioblastoma cell sensitivity to TMZ. In this project, we propose an innovative strategy involving the combination of 6-MP with TMZ for the treatment of glioblastoma.
Resection of glioblastoma in or near functional brain tissue is challenging because of the proximity of important structures to the tumor site. To pursue maximal resection in a safe manner, mapping methods have been developed to test for motor and language function during the operation. Previous evidence suggests that these techniques are beneficial for maximum safe resection in newly diagnosed grade 2-4 astrocytoma, grade 2-3 oligodendroglioma, and recently, glioblastoma. However, their effects in recurrent glioblastoma are still poorly understood. The aim of this study, therefore, is to compare the effects of awake mapping and asleep mapping with no mapping in resections for recurrent glioblastoma. This study is an international, multicenter, prospective 3-arm cohort study of observational nature. Recurrent glioblastoma patients will be operated with mapping or no mapping techniques with a 1:1 ratio. Primary 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 and 2) residual tumor volume of the contrast-enhancing and non-contrast-enhancing part as assessed by a neuroradiologist on postoperative contrast MRI scans. Secondary endpoints are: 1) overall survival (OS), 2) progression-free survival (PFS), 4) 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 will be carried out by the centers affiliated with the European and North American Consortium and Registry for Intraoperative Mapping (ENCRAM).
Glioblastoma multiforme (GBM), the most common and malignant primary brain tumor in adults is classified as a World Health Organisation (WHO) grade 4. Surgical removal of the tumor is the primary method of treatment. Unfortunately, because GBM is a disease of the entire brain, total resection is not possible. Therefore, the use of radiotherapy and/or chemotherapy is considered as Stupp protocol. Patients with recurrent GBM will be included in the ANCHIALE study. The goal of the trial is to evaluate the efficacy and tolerance of using the NanoTherm therapy system in recurrent GBM. The main questions it aims to answer are: 1. how NanoTherm therapy influences overall survival, and progression free survival; 2. what is the tolerance of NanoTherm therapy in terms of side effects (allergies, intracranial bleeding, infections, brain edema, increased intracranial pressure) and quality of life. Participants will undergo: - initial visit, considering the inclusion/exclusion criteria, neurological examination, and surveys regarding daily functioning and quality of life; - standard neurosurgical operation aimed, if possible, complete removal of the recurrent GBM and administration of NanoTherm ASI - a sterile suspension of iron oxide nanoparticles. A catheter will be implanted allowing for measurement of temperature during the first activation in the magnetic field; - between the 6th and 10th day after tumor resection, a standard computerized tomography (CT) scan of the head will be performed for routine postoperative evaluation; - after the first activation (10th day), the catheter will be removed; - subsequently, for 6 times, the patient will be subjected to the variable magnetic field of the NanoActivator® to induce hyperthermia - activations will be conducted on the 10th, 14th, 17th, 21st, 24th, and 28th day; - for up to 2 years post-procedure, a CT scan with an evaluation of treatment efficacy will be performed; - during follow-up visits for up to 2 years after the surgical procedure, a neurological examination, assessment of adverse symptoms, number of hospitalizations, number of medical visits, clinimetric assessment regarding quality of life, neurological deficit and degree of disability will be conducted. Researchers will compare NanoTherm group with patients undergoing Stupp protocol treatment for the abovementioned effects.
The purpose of this study is to determine if the investigational products, DB107-RRV and DB107-FC, as a combination treatment will shrink high-grade glioma (HGG) in patients with recurrent/progressive, resectable or unresectable disease and increase the time that disease is controlled.
The study evaluates safety, tolerability, pharmacokinetics at recommended phase II dose (RP2D) and preliminary antitumor activity of Niraparib + dd-TMZ "one week on, one week off" in patients affected by recurrent GBM IDH wild-type and recurrent IDH mutant (WHO grade 2-4) gliomas. The treatment will be administered until progressive disease, unacceptable toxicity, consent withdrawal, lost to follow-up or death. The entire study is expected to last approximately 40 months.
This is a single-center, open-label, multi-dose phase I clinical trial evaluating the safety, tolerability, and preliminary efficacy of ZSNeo-DC1.1, a personalized dendritic cell injection, in subjects with recurrent or progressive WHO grade III-IV gliomas post-standard treatment. The subjects are adult GBM patients who have undergone surgical resection for recurrence. After the completion of reoperation, subjects will receive autologous DC vaccine treatments as scheduled. The autologous genetic-modification-free DC cells will be loaded with multiple tumor neoantigen peptides and administered (i.h) to subjects. After 3 injections, the investigator will review subject's tolerance and compliance. The DLT observation period spans from the initial injection to 21 days after the third injection, aligning with the activation of anti-tumor immune response. About 15 subjects will be enrolled. The study utilizes a fixed dose of 1×10^7 cells per injection and employs two immunization schedules A or B. The trial is conducted in two stages: Dose Confirmation Stage: Enrollment of six subjects with recurrent or progressive gliomas following standard treatment. Each subject receives six subcutaneous injections of ZSNeo-DC1.1. Utilization of a standard "3+3" design for fixed dose confirmation and exploration of immunization schedules A and B. Dose Expansion Stage: Enrollment of at least six subjects with recurrent or progressive gliomas post-standard treatment. Administration of six subcutaneous injections of ZSNeo-DC1.1 to each subject, further investigating the safety and preliminary efficacy of ZSNeo-DC1.1 injection.
As a part of molecular imaging, many PET tracers have been investigated in this regard. Those include 18F-FDG being glucose analogue, 18F-FLT representing nucleoside metabolism, and 18F-FDOPA, 18F-FET, 11C-MET as amino acids analogues. Among these, 18F-FDG is the most commonly used tracer due to its broader use and easy availability. However, high physiological uptake in the brain is a significant limitation. The main limitation of other tracers is the need for onsite cyclotrons for their production, making their availability difficult. So, the search for an ideal modality is still ongoing, and the latest addition to this search is a radio ligand labeled Prostate Specific Membrane Antigen (PSMA). It is a new but potentially promising radiotracer, currently showing its utility in different malignancies. Investigators, therefore, aim to identify whether Ga-68 PSMA PET-CT has better diagnostic accuracy in the detection of recurrent gliomas than conventional imaging modalities.
This trial is a translational, open-label, monocentric prospective study of 80 patients aiming to study resistance mechanisms as well as biomarkers of resistance or sensitivity to TTFields. The study will be conducted on a population of patients with newly diagnosed glioblastoma treated with radio-chemotherapy followed by TTFields in the context of either routine care or a clinical trial. In this study, the Optune® system (battery operated device which delivers TTFields to the brain) will not be under investigation. For each included patient, blood samples will be collected during baseline visit (before initiation of radio-chemotherapy), then before initiation of TTFields and every 3 months during TTFields treatment. Additional blood samples will be scheduled at recurrence (if applicable). Moreover, tumor samples (formalin paraffin embedded (FFPE) tumor block and fresh samples) will be collected from surgery specimen on primary tumor by the sponsor for analysis. In case of recurrence, and if a second surgery is possible, tumor samples will also be collected. Tumor samples will be collected from biopsies taken in the course of routine practice and from surgical specimens collected during surgical procedure. No additional biopsies will be performed for the study. Patients will be followed-up for time to progression and overall survival for a maximum duration of 24 months from the TTFields initiation. MRI performed by patients during the course of the study will be collected by the sponsor for additional future research purposes.
This is an open-label, single-arm, phase II clinical trial to explore the efficacy and safety of low-dose radiotherapy combined with programmed death 1 (PD-1) inhibitor (sintilimab) and temozolomide in recurrent glioblastoma. The eligible patients are scheduled to administered sintilimab 200mg D1 Q3W temozolomide 50mg/m2 QD and radiotherapy 1Gy/1F D1/D2/D8/D15 Q3W for 4-6 cycles, then sintilimab for maintenance. The overall primary study hypothesis is that the combination regimen of low-dose radiotherapy, sintilimab and temozolomide is safe and feasible in the treatment of recurrent glioblastoma.