Active clinical trials for "Glioma"

Immune checkpoint blockade therapies targeting the immunomodulatory effect of cytotoxic T-lymphocyte antigen (CTLA-4) and programmed cell death-1/ Programmed death-ligand 1 (PD-1/PD-L1) have recently demonstrated survival benefit and durable response in phase III trials in several human cancers, especially in tumors that bear high mutation load and/or tumor-associated neoantigen signatures. The aim of these treatments is to restore effector T-cell function and antitumor activity, which could be enhanced in the context of high mutational/neoantigen load. In Isocitrate DeHydrogenase mutated High Grade Gliomas (IDHm HGGs), acquired resistance to alkylating chemotherapy frequently results from the inactivation of mismatch-repair (MMR) proteins which in turn leads to the acquisition of a hypermutator phenotype. These findings suggest that at least in a subset of recurrent IDHm HGGs immune checkpoint blockade therapies may be particularly effective. IDHm HGGs most frequently occur in young adults. The first line treatment consists of maximal safe surgical resection followed by radiotherapy and adjuvant alkylating chemotherapy (Temozolomide or Procarbazine-CCNU-Vincristine regimen (PCV)). Despite these treatments, most IDHm HGGs recurred in few years. There is no standard of care at recurrence and the median overall survival after it is less than 3 years. The investigators make the hypothesis that treatment with the anti-PD-1 monoclonal antibody Nivolumab will improve 24 weeks progression-free survival in IDHm HGGs that have recurred after initial treatment with radiotherapy and alkylating chemotherapy.

The purpose of this study is to determine the feasibility and safety of administering CMV RNA-pulsed dendritic cells (DCs), also known as CMV-DCs, to children and young adults up to 35 years old with nWHO Grade IV glioma, recurrent malignant glioma, or recurrent medulloblastoma. Evidence for efficacy will also be sought. This will be a phase 1 study evaluating CMV-DC administration with tetanus toxoid (Td) preconditioning and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) adjuvant in children and young adults up to 35 years old with WHO grade IV glioma, recurrent malignant glioma, or recurrent medulloblastoma. This safety study will enroll a maximum of 10 patients.

Postoperative conventional radiation at 60 Gy/30f is currently still considered the standard radiotherapy mode for high-grade gliomas; however, the efficacy is still unsatisfactory. Studies in recent years have shown that hypofractionated simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) has certain survival benefits over other fractionation methods; but, the best hypofractionation mode and its efficacy have not been confirmed. The purpose of this study is to investigate the maximum tolerated dose (MTD) of hypofractionated SIB-IMRT with stepwise escalating of doses combined with temozolomide (TMZ) for the treatment of malignant gliomas.

Pediatric high-grade gliomas are highly aggressive and treatment options are limited. The purpose of this first-in-pediatrics study is to examine the safety, tolerability, and pharmacokinetics of GDC-0084 and to estimate its maximum tolerated dose (MTD) when administered to pediatric patients with diffuse intrinsic pontine glioma (DIPG) or other diffuse midline H3 K27M-mutant gliomas after they have received radiation therapy (RT). GDC-0084 is a brain-penetrant inhibitor of a growth-promoting cell signaling pathway that is dysregulated in the majority of diffuse midline glioma tumor cells. This study is also designed to enable a preliminary assessment of the antitumor activity of single-agent GDC-0084, in the hope of enabling rational combination therapy with systemic therapy and/or radiation therapy (RT) in this patient population, which is in desperate need of therapeutic advances. Primary Objectives To estimate the maximum tolerated dose (MTD) and/or the recommended phase 2 dosage (RP2D) of GDC-0084 in pediatric patients with newly diagnosed diffuse midline glioma, including diffuse intrinsic pontine glioma (DIPG) To define and describe the toxicities associated with administering GDC-0084 after radiation therapy (RT) in a pediatric population To characterize the pharmacokinetics of GDC-0084 in a pediatric population Secondary Objectives To estimate the rate and duration of radiographic response in patients with newly diagnosed DIPG or other diffuse midline glioma treated with RT followed by GDC-0084 To estimate the progression-free survival (PFS) and overall survival (OS) distributions for patients with newly diagnosed DIPG or other diffuse midline glioma treated with RT followed by GDC-0084

This research is being done to study the pattern of changes in various parts of the magnetic resonance imaging (MRI) studies that patients have done to help plan their radiation therapy and to evaluate the effects of therapy. The MRI of the brain is one of the major ways a participant's doctors determine how to treat a participant's tumor and if the participant's tumor is growing or not. In this study the investigators want to learn if new sequences added to the MRI that the investigators are already getting to guide partipants' radiation treatment can be analyzed to help make better treatment decisions. MRI sequences that examine the composition and structure of the tissues in the brain in a different way will be obtained. These are called called Amide Proton Transfer (APT) and Diffusion Weighted MRI. These scans will first be performed at the time of participants' radiation plannings scan done before treatment and near the end of the course of radiation treatments. This will allow the study team to investigate if there are changes in these sequences before radiation treatment and to see if using these MRI studies will allow us to better plan radiation treatments for patients in the future. This pre-treatment scan will be done at the same time as participants' standard radiation planning MRI, but will cause the scan to take longer. Participants will also have an extra MRI during one of the last 5 days of the planned 28-33 radiation treatments that are standardly used. This additional scan will not include administration of injected contrast agents, and would occur on a day when participants are also coming in for radiation. This scan will be compared with the first scan. The investigators will determine whether these changes may predict later long term outcome of treatment for patients. Patients who enroll in this study will get all of the standard therapy they would get for their tumor whether or not they participate in this study. There is no extra or different therapy given. The investigators anticipate that the radiation treatment volumes created using APT will largely overlap with the conventional plan but will be distinct at the margins. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Volume containing elevated APT signal may be associated with outcome (survival). In an exploratory analysis, the investigators will evaluate whether there are characteristic patterns that should be prospectively studied in a larger trial.

Radiation therapy is an important adjunct in the treatment of patients with glioma, although a common side effect is radiation-induced injury of brain parenchyma. Unfortunately, conventional MRI is not accurate in differentiating radiation-induced brain injury from recurrent tumour, both of which may demonstrate progressive contrast enhancement. Recent studies have suggested that perfusion MRI could improve this differentiation. Perfusion MRI can be performed with an injection of exogenous contrast using dynamic contrast enhancement (DCE) or dynamic susceptibility contrast enhancement (DSC). Perfusion MRI can also be performed without contrast injection using arterial spin labeling (ASL) or intravoxel incoherent motion (IVIM). DCE-MRI relies on accurate measurement of T1 values in order to convert the MRI signal intensity to contrast concentration. Dynamic susceptibility-weighted contrast enhancement (DSC) perfusion is the most common technique used in clinical practice but measurement of tumor relative cerebral blood volume (rCBV) can be biased by extravascular contrast leakage and susceptibility-weighted artifacts. The purpose of this study is to evaluate the accuracy of perfusion MR imaging using non-contrast and contrast-based techniques in differentiating recurrent tumour from radiation-induced brain injury in patients with known high grade glioma. The investigators will compare the accuracy of IVIM, ASL, DCE and DSC techniques. A secondary goal of the study is to compare two new different T1 mapping methods used for DCE-MRI.

The goal of this observational study is to evaluate disease-free survival (DFS) in patients with malignant gliomas undergoing neurosurgical procedures using 5-aminolevulinic acid (5-ALA)-based photodynamic therapy

The use of intraoperative ultrasound (IOUS )seems to have significantly increased the Gross total Resection rate achieved in brain gliomas surgery. As regard intraoperative visualisation of the tumor and its residuals, the effectiveness of IOUS has been documented in a series of 192 High Grade glioma patients, in which the combination of neuronavigation and IOUS was also related to increased overall survival in a prospective study of 32 patients, documented a good level of agreement between intraoperative ultrasonography and postoperative contrast-enhanced MRI in detecting tumor residuel they concluded that the IOUS produces results similar to those of MRI, and therefore, can be used to maximize tumor resection.

This is a first-in-children phase 1 trial using indoximod, an inhibitor of the immune "checkpoint" pathway indoleamine 2,3-dioxygenase (IDO), in combination with temozolomide-based therapy to treat pediatric brain tumors. Using a preclinical glioblastoma model, it was recently shown that adding IDO-blocking drugs to temozolomide plus radiation significantly enhanced survival by driving a vigorous, tumordirected inflammatory response. This data provided the rationale for the companion adult phase 1 trial using indoximod (IND#120813) plus temozolomide to treat adults with glioblastoma, which is currently open (NCT02052648). The goal of this pediatric study is to bring IDO-based immunotherapy into the clinic for children with brain tumors. This study will provide a foundation for future pediatric trials testing indoximod combined with radiation and temozolomide in the up-front setting for patients with newly diagnosed central nervous system tumors.

Phase 1a/1b does-escalation study of cabiralizumab alone and with nivolumab in advanced solid tumors.