High Grade Glioma

This study is to provide access for patients who are receiving treatment with dabrafenib and/or trametinib in a Novartis-sponsored Oncology Global Development, Global Medical Affairs or a former GSK-sponsored study who have fulfilled the requirements for the primary objective, and who are judged by the investigator as benefiting from continued treatment in the parent study as judged by the Investigator at the completion of the parent study.

The goal of this clinical trial is to: 1) evaluate the safety, tolerability, and recommended dose of dexbrompheniramine when combined with metronomic temozolomide for adults with recurrent high-grade glioma who have been previously treated with standard of care chemoradiation therapy and 2) determine the efficacy of the combination therapy in adults with glioblastoma who progressed during the first six cycles of adjuvant standard dose temozolomide. The main questions it aims to answer are: * What medical problems to participants have when taking dexbrompheniramine together with temozolomide? * What is the correct dose of dexbrompheniramine to use when evaluating the safety and efficacy of the combination therapy? * Is the combination therapy more effective at delaying disease progression compared to temozolomide alone? Participants will take dexbrompheniramine and temozolomide every day at night.

The purpose of this study is to test the safety and efficacy of iC9-GD2-CAR T-cells, a third generation (4.1BB-CD28) CAR T cell treatment targeting GD2 in paediatric or young adult patients affected by relapsed/refractory malignant central nervous system (CNS) tumors. In order to improve the safety of the approach, the suicide gene inducible Caspase 9 (iC9) has been included.

Background: Glioblastoma is a common brain cancer in adults. Treatment includes surgery, radiation, and chemotherapy. But this cancer can return after treatment and is often fatal. Researchers want to know if a study drug (LMP744) can kill glioblastoma tumor cells. Objective: To test LMP744 in people with glioblastoma. Eligibility: People aged 18 years or older with glioblastoma that returned after treatment. Design: Participants will be screened. They will have a surgery to remove a small sample of tumor tissue (biopsy) from the brain. This will be done under protocol 03-N-0164. They will stay in the clinic for 1 night. They will also have imaging scans and tests of their heart function. Participants will have a central line installed: A flexible tube will be inserted into a vein in the chest. It will be attached to a "port" under the skin. This port will be used to draw blood and give medicines without having to insert new needles into a vein. LMP744 will be given through the central line for 5 days in a row. Participants will remain in the clinic for this time. Participants will then have a second surgery to remove as much of their tumor as possible. They will remain in the clinic until they recover from the surgery. Then they will recover at home after surgery. Participants will return to the clinic to receive the study drug for 5 days in a row through the central line, once a month for up to 12 months. Blood tests, heart function tests, and periodic imaging scans will be repeated during these visits. Participants will continue to have telehealth visits every 3 months after they stop taking the drug.

This is an open label, intra-patient dose escalation, to evaluate ADI-PEG 20, in combination with Temozolomide (TMZ) and radiation therapy (RT) in children, adolescents and young adult patients with newly diagnosed high grade glioma (HGG).

This is an open label, Phase 1b safety, dose-finding, brain tumor delivery, and pharmacokinetics study of intranasal NEO100 in patients with pediatric-type diffuse high grade gliomas. Patients will receive IN NEO100 that will follow a dose titration design, followed by a standard dose escalation design to establish safety. Brain tumor delivery of NEO100 will be confirmed in each disease sub-type by surgical resection/needle biopsy only if clinically indicated and scheduled for clinical purposes and testing with residual tissue for NEO100 and the major metabolite of NEO100 (Perillic Acid).

This is a phase I study to assess the safety and feasibility of IL-8 receptor modified patient-derived activated CD70 CAR T cell therapy in newly diagnosed and recurrent CD70+ Pediatric High-Grade Gliomas (pHGG) and Diffuse Intrinsic Pontine Glioma (ndDIPG)

The goal of this study is to further evaluate feasibility and tolerability of Opdualag for patients with replication repair deficient HGG, including DIPG.

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 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.

This study will address the question of whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in pediatric patients with newly-diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) as well as recurrent medulloblastoma (MB). PEP-CMV is a vaccine mixture of a peptide referred to as Component A. Component A is a synthetic long peptide (SLP) of 26 amino acid residues from human pp65. The SLPs encode multiple potential class I, class II, and antibody epitopes across several haplotypes. Component A will be administered as a stable water:oil emulsion in Montanide ISA 51. Funding Source - FDA OOPD

This feasibility study will assess the clinical potential of a new imaging approach to detect viable high grade glioma (HGG) in pediatric and adult patients after standard of care radiation therapy (RT) with or without concurrent temozolomide (TMZ). Study participants will undergo simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) with O-(\[2-\[F-18\]fluoroethyl)-L-tyrosine (FET, amino acid transport) and 1H-1-(3-\[F-18\]fluoro-2-hydroxypropyl)-2-nitroimidazole (FMISO, hypoxia) at the time of standard of care imaging after completion of RT. The presence of viable tumor at this time point will be assessed on a per patient basis. Study participants will be followed clinically and with standard of care (SOC) imaging for up to 2 years after completion of PET/MRI to determine the nature of lesions seen on investigational imaging and to obtain patient outcome data. The imaging data will also be used to develop a semi-automated workflow suitable for implementation in clinical trials and standard of care PET/MRI studies.

The purpose of this research study is to see if investigators can predict how brain functioning changes after radiation treatment based on PET scans and blood tests. Most participants experience at least mild decreases in their memory or attention after radiation therapy. Investigators hope that PET scans, optional lumbar puncture, and blood tests might help investigators predict who might have larger changes in their brain function after radiation.

The purpose of this study is to test the safety and feasibility of recording brain activity within and around high-grade glioma tumors at the time of surgery. A small biopsy will be taken at the sites of the recordings.

In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare high-grade glioma that expresses GD2. Cohort 2 is for patients with a type of cancer called progressive diffuse intrinsic pontine glioma that expresses GD2. Because there is no standard treatment at this time, patients are asked to volunteer in a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that help the body fight infection. This research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat cancer patients. They have shown promise but have not been strong enough to cure most patients. Researchers have found from previous research that they can put a new antibody gene into T cells that will make them recognize cancer cells and kill them. GD2 is a protein found on several different cancers. Researchers testing brain cancer cells found that many of these cancers also have GD2 on their surface. In a study for neuroblastoma in children, a gene called a chimeric antigen receptor (CAR) was made from an antibody that recognizes GD2. This gene was put into the patients own T cells and given back to 11 patients. The cells did grow for a while but started to disappear from the blood after 2 weeks. The researchers think that if T cells are able to last longer they may have a better chance of killing tumor cells. In this study, a new gene will be added to the GD2 T cells that can potentially cause the cells to live longer. T cells need substances called cytokines to survive. The gene C7R has been added that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. In other studies using T cells researchers found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and it will allow the T cells to expand and stay longer in the body and potentially kill cancer cells more effectively. After treating 11 patients, the largest safe dose of GD2-CAR T cells given in the vein (IV) was determined. We are now combining an IV infusion with an infusion directly into the brain through the Ommaya reservoir or programmable VP shunt. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way. Patients will now be assigned to Cohort 1 and 2 based on their tumor type. The GD2.C7R T cells are an investigational product not approved by the FDA. The purpose of this study is to combine infusions into the vein in the first treatment cycle with infusions directly into the cerebrospinal fluid (CSF) in the brain (intracerebroventricularly) through the ommaya reservoir or programmable VP shunt for infusions cycles 2-24. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way, and additionally to evaluate how long they can be detected in the blood and CSF and what affect they have on brain cancer.

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.

The goal of this interventional study is to Assess the safety and tolerability of atovaquone in combination with standard radiation therapy (RT) for the treatment of pediatric patients with newly diagnosed pediatric high-grade glioma/diffuse midline glioma/diffuse intrinsic pontine glioma (pHGG/DMG/DIPG). The secondary aim is to assess the safety and tolerability of longer-term atovaquone treatment for pediatric patients with relapsed or progressed pHGG/DMG/DIPG and medulloblastoma (MB) or pHGG/DMG/DIPG after completion of RT and before progression.

This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4 to \<12 years (Phase I) or 12 to \</=39 years (Phase II) to test its safety and efficacy, respectively. Funding Source - FDA OOPD (grant number FD-R-0532-01)

The primary objective of this study is to determine the safe dose range of NRG-103 in patients and to recommend the dosage for subsequent treatment, while also evaluating the preliminary efficacy and tolerability of the product.

A single-arm clinical study on the efficacy and safety of the novel oncolytic virus Ad-TD-nsIL12 combined with PD-1 inhibitors in the treatment of recurrent high-grade glioma

Pediatric gliomas harboring BRAF-alterations, commonly BRAFV600 mutation or KIAA1549-BRAF fusion, are currently treated with either chemotherapy or mitogen activated protein kinase (MAPK) inhibitors, such as, dabrafenib and/or trametinib. Unfortunately, some BRAF-altered gliomas can progress or have rebound growth after discontinuation of therapy. Data from BRAFV600E-mutant melanoma has shown potential synergy between MAPK inhibition and anti-programmed cell death 1 (anti-PD1) checkpoint blockade. Anti-PD1 therapy, such as, nivolumab can block the PD1 receptor on T cells, a marker of T cell exhaustion, allowing a continued or more robust anti-tumor immune response. Here, investigators will combine MAPK inhibition with anti-PD1 therapy in recurrent, refractory low grade BRAF-altered glioma and newly diagnosed or recurrent BRAF-altered or NF-altered high grade glioma.

High-grade gliomas (HGGs) are among the most aggressive and treatment-resistant brain tumors. Immunotherapy with checkpoint inhibitors like nivolumab has shown promise, but its efficacy remains variable and poorly understood in this patient population. This clinical trial investigates a novel imaging-enabled formulation of nivolumab-IRDye800 (nivo800) which incorporates a near-infrared (NIR) fluorescent dye to enable real-time visualization of drug distribution within tumor tissue.

The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.

The primary objective will be to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in (Stratum 1) adult patients with newly diagnosed GBM (MGMT low level or unmethylated in adults only) and (Stratum 2) in pediatric patients with newly diagnosed HGG (pHGG). Funding Source - FDA OOPD

The purpose of this study is to determine whether newly diagnosed high-grade glioma(s) that cannot be removed surgically change as a result of the study treatment; and to identify and evaluate the potential side effects (good and bad) of the study treatment in patients with newly diagnosed high-grade glioma(s) that cannot be removed surgically.