Metastatic Brain Tumor

The goal of this study is to determine the efficacy of the study drugs tovorafenib to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (MAPK) that this drug targets. The main question the study aims to answer is whether tovorafenib can prolong the life of patients diagnosed with HGG, including DIPG.

This is a Phase 2, open-label, single-arm clinical study designed to evaluate the efficacy and safety of Belvarafenib in patients with BRAF-altered primary brain tumors (Cohort 1) and metastatic brain tumors (Cohort 2). Eligible patients are those with a confirmed BRAF alteration identified by next-generation sequencing (NGS). Patients who meet the eligibility criteria will receive a detailed explanation of the study, including its purpose, procedures, potential benefits, and risks. Only patients who voluntarily provide written informed consent will be enrolled. All enrolled patients will receive Belvarafenib monotherapy at a dose of 450 mg twice daily (BID). The study drug will be taken orally within 30 minutes after meals with at least 200 mL of water, preferably at approximately 12-hour intervals each day. One treatment cycle is defined as 28 consecutive days of continuous dosing without a planned treatment break. Patients will receive treatment for six cycles (approximately six months) as the initial treatment period. Treatment may be extended or discontinued earlier at the investigator's discretion based on clinical benefit, disease status, and tolerability. During the study, patients will undergo regular clinical evaluations, including physical examinations, vital sign assessments, laboratory tests, and monitoring for adverse events. Radiologic assessments using MRI and/or CT will be performed at scheduled intervals to evaluate tumor response and disease progression. The study aims to determine whether Belvarafenib can control tumor growth, delay disease progression, and improve clinical outcomes in patients with BRAF-altered brain tumors. If treatment-related toxicities occur, dose reductions are permitted according to the protocol. The dose may be reduced from 450 mg BID to 300 mg BID, and subsequently to 200 mg BID, if clinically indicated. Temporary treatment interruption may also be implemented until toxicity resolves. If unacceptable toxicity persists despite dose modification, treatment will be permanently discontinued. Study treatment may be discontinued if any of the following occurs: confirmed disease progression, unacceptable toxicity, withdrawal of informed consent, inability to comply with the study protocol, receipt of other anticancer therapies that may interfere with study outcomes, or if the investigator determines that continued treatment is no longer in the patient's best interest. However, if radiologic disease progression is observed but the investigator determines that the patient continues to derive clinical benefit, treatment beyond progression may be considered after discussion with the sponsor, with appropriate documentation of the rationale. After discontinuation of study treatment, patients will receive the most appropriate subsequent management, including best supportive care (BSC) or other anticancer therapies, as determined by the treating investigator. Follow-up assessments will continue according to the study protocol. The primary objective of this study is to evaluate the efficacy of Belvarafenib in patients with BRAF-altered primary and metastatic brain tumors, while also assessing its safety profile. The results of this study are expected to provide important clinical evidence supporting the development of new treatment strategies for patients with BRAF-altered brain tumors.

The goal of this study is to determine the efficacy of the study drug olutasidenib to treat newly diagnosed pediatric and young adult patients with a high-grade glioma (HGG) harboring an IDH1 mutation. The main question the study aims to answer is whether the combination of olutasidenib and temozolomide (TMZ) can prolong the life of patients diagnosed with an IDH-mutant HGG.

The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor.

The goal of this study is to determine the efficacy of the 1) ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K/mTOR) that these drugs target or 2) ribociclib and temozolomide to treat pediatric and young adult patients newly diagnosed with diffuse hemispheric glioma (DHG), H3G34-mutant. The main question the study aims to answer is whether the combinations of ribociclib and everolimus or ribociclib and temozolomide can prolong the life of patients diagnosed with HGG/DIPG or DHG H3G34-mutant.

The purpose of this study is to develop and test a new magnetic resonance imaging (MRI) technique to see if it can be used to tell the difference between tumor growth from worsening of cancer and growth from the effects of treatment in participants who have brain tumors treated with radiation therapy called stereotactic radiosurgery (SRS).

Imaging procedures such as 1-(2-\[18F\]FLUOROETHYL)-L-Tryptophan PET/CT in patients with cancers may help doctors assess a patient's response to treatment and help plan the best treatment in the future. The purpose is to see if there can be a better differentiation of tumor and non-tumor tissue where the tumor tissue has a higher uptake of Tryptophan.

Purpose of the study: AIM 1: Prospectively collect pre-operative \[functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), magnetoencephalography (MEG)\] and intra-operative mapping data in patients with intra-axial brain tumors to assess how well each modality predicts the location of eloquent brain function. In addition, each modality will be compared with the other. AIM 2: Assess reorganization of eloquent brain function and plasticity in patients with intra-axial brain tumors. This will be accomplished by prospectively collecting post-operative mapping studies and neuropsychological tests to compare them to prior mapping studies as stated above.