Clinical Research Directory

A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden

This phase II trial studies the effect of immunotherapy drugs (ipilimumab and nivolumab) in treating patients with glioma that has come back (recurrent) and carries a high number of mutations (mutational burden). Cancer is caused by changes (mutations) to genes that control the way cells function. Tumors with high number of mutations may respond well to immunotherapy. Immunotherapy with monoclonal antibodies such as ipilimumab and nivolumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving ipilimumab and nivolumab may lower the chance of recurrent glioblastoma with high number of mutations from growing or spreading compared to usual care (surgery or chemotherapy).

Vorasidenib Guided by AGX PET in Recurrent/Low-grade Glioma

The goal of this prospective, single-arm, open-label clinical trial is to evaluate whether 18F-AGX PET imaging can be used to assess early treatment response and metabolic changes in adult patients with recurrent or residual WHO 2021 grade 2-3 IDH-mutant diffuse glioma receiving Vorasidenib therapy. IDH-mutant diffuse gliomas often show slow tumor growth, making early treatment response difficult to evaluate using conventional structural imaging such as magnetic resonance imaging (MRI). Clinical endpoints such as progression-free survival (PFS) and overall survival (OS) typically require long follow-up periods to detect treatment effects. Therefore, the development of sensitive and noninvasive imaging methods for early evaluation of therapeutic response is needed. This study aims to determine whether metabolic changes detected by 18F-AGX PET during Vorasidenib treatment are associated with tumor structural changes and clinical outcomes. The main questions it aims to answer are: * Whether early changes in tumor metabolic activity measured by 18F-AGX PET, including percentage change in maximum tumor-to-background ratio (TBRmax), are associated with changes in tumor growth rate (TGR) measured by MRI during treatment. * Whether early metabolic response detected by 18F-AGX PET imaging after initiation of Vorasidenib treatment can predict subsequent disease progression or tumor growth dynamics. Participants enrolled in this study will receive oral Vorasidenib once daily for 12 treatment cycles (28 days per cycle), with dosing based on body weight. Participants will: * Undergo baseline MRI and 18F-AGX PET imaging following surgery for recurrent or residual disease. * Receive oral Vorasidenib continuously for 12 cycles. * Undergo MRI scans at baseline and during treatment cycles 1, 2, 3, 6, 9, and 12 to assess structural tumor changes. * Undergo 18F-AGX PET/CT scans at baseline and during treatment cycles 1, 2, 3, 6, and 12 to assess metabolic tumor activity. * Provide serial blood samples for laboratory safety monitoring, including hematologic and biochemical testing. * Undergo magnetic resonance spectroscopy (MRS) to quantify intratumoral 2-hydroxyglutarate (2-HG) levels as an indicator of IDH mutation-associated metabolic activity. Participants will be followed for imaging-based disease progression using RANO criteria and for treatment-related adverse events during the study period. This study will evaluate the feasibility of using 18F-AGX PET imaging as a noninvasive imaging biomarker for early response assessment in IDH-mutant diffuse glioma patients receiving targeted IDH inhibition therapy with Vorasidenib.

18F-Fluciclovine PET-MRI in High-grade Glioma

The purpose of this study is to see if 18F-fluciclovine (Axumin®) PET imaging is useful and safe in the management of children with High Grade Gliomas. Investigators seek to determine if this imaging will help doctors tell the difference between tumor growth (progression) and other tumor changes that can occur after treatment.

Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma

This early phase I trial studies brain tumor (glioma) metabolism in response to eflornithine (DFMO) and polyamine transport inhibitor AMXT-1501 dicaprate (AMXT 1501) in patients with diffused or high grade glioma. Brain tumors use and produce certain molecules to survive and grow. DFMO is an irreversible inhibitor of ornithine decarboxylase, the enzyme catalyzing polyamine synthesis. AMXT 1501 is a polyamine transport inhibitor which prevents uptake of polyamines from the extracellular environment. This trial is being done to analyze how DFMO and AMXT 1501 affect brain tumor metabolism based on the molecules in the tumor's fluid.

Proton Versus Photon Radiotherapy in Adults With Primary Brain Tumors

This study will be done in adults with brain tumors having good prognosis requiring treatment with radiotherapy. The current practice for brain radiotherapy involves treatment using X rays (photon radiotherapy). Proton beam therapy is a more advanced form of delivering radiation, which allows the reduction of the dose of radiation to the parts of the brain surrounding the tumor. After treatment with photon radiotherapy, certain late effects of radiation, like memory decline, hormonal deficits, hearing loss, and worsening of neurological function, can occur in some patients. From the evaluation of dose profiling, proton beam therapy has the potential to reduce the possibility of side effects by reducing the dose to critical organs. However, there is no clinical data to demonstrate whether the theoretical dose reduction translates to a clinically meaningful benefit. In the proposed study, 156 patients will be randomly allocated to either proton or photon radiotherapy in 1: 1 ratio. The primary objective of the study is to explore whether proton therapy improves functional survival, which is life expectancy without recurrence, death, or complications from radiotherapy.

Glioma Adaptive Radiotherapy With Development of an Artificial Intelligence Workflow

Gliomas are common primary brain tumors in adults. Gliomas can be classified into different types based on tumor grade, histopathological features, and molecular characteristics. The common types of diffuse gliomas include glioblastoma, astrocytoma, and oligodendroglioma. The standard treatment for diffuse gliomas includes surgery followed by radiation and chemotherapy. As per standard institutional practice, a uniform dose of radiation is delivered to the disease area and MRI is done before and after the treatment. In this study, MRI and PET scan will be done before starting the treatment and standard dose of radiation will be delivered. The interval imaging will be done twice during the course of treatment with MRI and PET, followed by dose modifications. The CT, MRI, and PET will be combined. Based on PET imaging, specific dose will be altered and delivered to specific areas. Dose modification will be done with the help of artificial intelligence. Participant's assessment will be done at regular intervals. Modifications in radiation plans are done based on the changes in disease seen in scans is likely to improve the accuracy of RT treatments. Dose modifications based on imaging to resistant areas will help achieve better tumor control, reduce treatment-related toxicities, precise delivery of the RT and adjusting doses to the organs at risk (OAR) and changes in disease leading to better treatment compliance. Creating an artificial intelligence framework in radiation oncology promises to improve quality of workflow, treatment planning and RT delivery. The aim of the study is to develop an artificial intelligence workflow for treatment of glioma with adaptive radiotherapy. This study will be conducted in Tata Memorial Centre on a population of 60 patients for a duration of 2 years. The total study duration is 4 years.

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma

Multicenter, open-label, single-arm Phase 1/2 study on the safety and efficacy of the combination of NMS-03305293 and temozolomide (TMZ) in adult patients with diffuse gliomas (Phase 1) and isocitrate dehydrogenase (IDH) wild type glioblastoma (Phase 2) at first relapse.

A Study of Chlorophyllin for the Management of Brain Radio-necrosis in Patients With Diffuse Glioma

Diffuse gliomas are common tumors involving the brain. They are usually treated by surgery followed by radiation and chemotherapy. Radiotherapy is used for the treatment of brain tumors which causes damage to the tumor cells. However, radiotherapy can also affect the surrounding healthy cells in the brain, causing inflammation and swelling in the region, which is known as radio necrosis (RN). This is considered a late side effect of radiation and is seen in 10-25% of patients treated with radiation for brain tumors. Sometimes, radionecrosis can be detected on routine imaging during follow-up without new symptoms (asymptomaticRN). At the same time, in some patients, it can give rise to new symptoms like headaches, weakness, seizures,etc (symptomatic RN). The standard treatment of RN includes steroid medicines called dexamethasone, which is helpful in a proportion of patients. This is a prospective phase 2 study. This study is being conducted to investigate the ability of the drug Chlorophyllin in the treatment of radionecrosis. Chlorophyllin is a water-soluble compound obtained from the green plant pigment called chlorophyll. It has been shown to have anti-cancer, anti-bacterial, anti-viral, anti-inflammatory, and antioxidant properties. It is also used as an oral formulation and is an over-the-counter drug in various countries, and also as a food colouring agent. This is the first time chlorophyllin will be used in the setting of brain radionecrosis. Our primary aim of the study is to assess whether CHL will improve the clinical-radiological response rates. This study will be conducted on a population of 118 patients for a duration of 3 months. The total study duration is 2 years. The study is funded by Bhabha Atomic Research Centre (BARC).

RE-irradiation of Diffuse MIdline Glioma paTients

The REMIT (RE-irradiation of diffuse MIdline glioma paTients) study evaluates safety and the palliative efficacy of re-irradiation of patients with diffuse midline glioma (DMG). The study will introduce a standard re-irradiation treatment schedule for DMG patients who have progressed following primary treatment.