Glioma

The purpose of this study is to see if combining silevertinib with temozolomide after surgery and radiotherapy helps treat newly diagnosed glioblastoma (GBM) better than using temozolomide alone in the maintenance setting. Specifically, this study is being done to find answers to the following questions: * How much of the study drugs (silevertinib combined with temozolomide) should be given to participants with GBM? * What are the side effects participants have when taking the study drug (silevertinib combined with temozolomide)? * Can the study drug (silevertinib combined with temozolomide) help participants with GBM live longer without disease progression compared to treatment with temozolomide alone?

This study performs standardized testing of tumor tissue samples to learn which genes are mutated (have changed) in order to provide personalized cancer therapy options to cancer patients at MD Anderson. This may help doctors use testing information on tumors to identify clinical trials that may be most relevant to patients. Researchers may also use the information learned from this study to develop a database of the different kinds of mutations in cancer-related genes.

This substudy will investigate a new imaging approach using positron emission tomography (PET) and two investigational drugs (\[18F\]FET and \[18F\]FMISO) to see if the imaging results will help with the placement of catheters for therapy delivery in 20 adult patients with malignant gliomas (MGs) who are participating in the UAB IRB approved main study, A Phase I/II Study of Pembrolizumab and M032 (NSC 733972), a Genetically Engineered HSV-1 Expressing IL-12, in Patients with Recurrent/Progressive and Newly Diagnosed Glioblastoma Multiforme, grade 3 or grade 4 astrocytoma, or Gliosarcoma (IRB 300007756 PI Markert). The PET and MR imaging results will be available to guide catheter placement within IRB 300007756 study-specific guidelines during Neurosurgery.

This clinical trial evaluates the use of microdialysis catheters during surgery to collect biomarkers, and studies the feasibility of intra- and post-operative microdialysis during neurosurgery for central nervous system malignancies. A biomarker is a measurable indicator of the severity or presence of disease state. Information collected in this study may help doctors develop new strategies to better diagnose, monitor, and treat brain tumors.

This clinical trial is looking at two drugs called dabrafenib and trametinib. Dabrafenib and trametinib are approved as standard of care treatment for adult patients with melanoma (a type of skin cancer) or lung cancer and in children with glioma (a type of brain tumour). This means they have gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Dabrafenib and trametinib work in patients with a particular mutation in their cancer known as BRAF V600. Investigators now wish to find out if they will be useful in treating patients with other cancer types which have the same mutation. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.

Background: Glioblastoma (GBM) is a cancer of the brain. Current survival rates for people with GBM are poor; survival ranges from 5.2 months to 39 months. Most tumors come back within months or years after treatment, and when they do, they are worse: Overall survival drops to less than 10 months. No standard treatment exists for people whose GBM has returned after radiation therapy. Objective: To find a safe schedule for using radiation to treat GBM tumors that returned after initial radiation treatment. Eligibility: People aged 18 years and older with grade 4 GBM that returned after initial radiation treatment. Design: Participants will be screened. They will have a physical exam with blood tests. A sample of tumor tissue may be collected. Participants will undergo re-irradiation planning: They will wear a plastic mask over their head during imaging scans. These scans will pinpoint the exact location of the tumor. This spot will be the target of the radiation treatments. Participants will undergo radiation treatment 4 times per week. Some people will have this treatment for 3 weeks, some for 2 weeks, and some for 1 week. Blood tests and other exams will be repeated at each visit. Participants will complete questionnaires about their physical and mental health. They will answer these questions before starting radiation treatment; once a week during treatment; and at intervals for up to 3 years after treatment ends. Participants will have follow-up visits 1 month after treatment and then every 2 months for 6 months. Follow-up clinic visits will continue up to 3 years. Follow-ups by phone or email will continue an additional 2 years.

The purpose of this clinical trial is to learn the safety and effects of the study medicine (PF-07799544) alone or in combination as a potential cancer treatment for adults with advanced solid tumors. The study will be conducted in two parts: PF-07799544 as a single agent (Phase 1a) and PF-07799544 in combination with another study medicine called PF-07799933 (Phase 1b). Phase 1a is no longer open for enrollment. In Phase1b (noted as "this study"), we are seeking participants who have: * a solid tumor which is metastatic or recurrent (excluding colorectal cancer) * tumor with the mutation (abnormal gene) called "BRAF V600" * received required prior treatment for cancer per cohort assigned. All participants in this study will receive both study medicines. Both study medicines are tablets that are taken by mouth at home twice a day. Participants will receive study medicines until their cancer is no longer responding, unacceptable side effects, or 2 years. Participants may continue to receive study therapy beyond 2 years. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.

Background: About 90,000 new cases of brain and spinal cord tumors are diagnosed annually in the United States. Most of these tumors are benign; however, about 30% are malignant, and 35% of people with malignant tumors in the brain and spinal cord will die within 5 years. Many of these people have changes in certain genes (MYC or MYCN) that drive the development of their cancers. Objective: To test a study drug (PLX038) in people with tumors of the brain or spinal cord. Eligibility: People aged 18 years or older with a tumor of the brain or spinal cord. Some participants must also have tumors with changes in the MYC or MYCN genes. Design: Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and a test of their heart function. They may need to have a biopsy: A sample of tissue will be removed from their tumor. PLX038 is given through a tube attached to a needle inserted into a vein in the arm. All participants will receive PLX038 on the first day of each 21-day treatment cycle. They will take a second drug 3 days later to help reduce the risk of infection; for this drug, participants will be shown how to inject themselves under the skin at home. Blood tests, imaging scans, and other tests will be repeated during study visits. Hair samples will also be collected during these visits. Some participants may have an additional biopsy. Study treatment will continue up to 7 months. Follow-up visits will continue every few months for up to 5 years.

This study will include up to 40 participants with Grade 2 or Grade 3 IDH1-mutant glioma who have undergone surgery and received vorasidenib as their only treatment, experienced radiographic disease progression on vorasidenib (confirmed by Blinded Independent Central Review \[BICR\] per modified Response Assessment in Neuro-Oncology \[RANO\] 2.0), and are not in need of immediate chemotherapy or radiotherapy.

This study (1438-0003) is open to adults with a tumour in the brain that is positive for the tumour marker delta-like 3 (DLL3). This study is in people with advanced cancer for whom previous treatment was not successful. The purpose of this study is to find out the highest dose of BI 764532 that people with a brain tumour that is positive for DLL3 can tolerate. BI 764532 is an antibody-like molecule that can attach and link together the cancer cells and T-cells of the immune system (DLL3/CD3 bispecific). This may help the immune system fight cancer. Participants get BI 764532 infusions into a vein when starting treatment. If there is benefit for the participants and if they can tolerate it, the treatment is continued. During this time, participants visit the study site at regular intervals. The total number of visits depends on how they respond to and tolerate the treatment. The first study visits include staying to monitor participants' safety. Doctors record any unwanted effects and regularly check the general health of the participants.

A open-label drug-drug interaction (DDI) study to evaluate the effects of olutasidenib on the pharmacokinetics (PK) of a CYP450 and OATP1B1 probe substrate cocktail in participants with IDH1 mutation-positive malignancies.

To compare the efficacy and safety of Lenvatinib combined with the standard Stupp regimen versus the standard Stupp regimen alone in the treatment of newly diagnosed glioblastoma with MGMT promoter methylation positive.

This clinical trial tests how well a digital treatment platform using a mobile application works for the delivery of home-based sequential therapy in patients with glioma. Access to specialized neuro-oncology care in the United States for patients with glioma is critically deficient. Care at centers with neuro-oncology specialists is associated with improved survival outcomes, yet many patients have limited access due to distance, disease-related disability, or lack of financial resources. The application provides patients continuous access to their care team in the home setting. A digital treatment platform may increase clinical trial participation and accelerate development of novel therapeutics while addressing a great health disparity in patients with glioma.

Patients with grade 2 and 3 gliomas who received photon radiation therapy as part of their standard treatment are at risk of developing cognitive impairments, depending on the tumor's location and the size of the target volume. The extent to which these are caused in individual cases by the brain tissue within the target volume, which is necessarily exposed to a high dose, or whether they can be modified by differences in the exposure of surrounding brain regions exposed to low or moderate doses, is unknown. With the help of proton therapy, the risk of neurocognitive dysfunction could potentially be reduced by decreasing the brain volumes outside the target volume that are exposed to radiation therapy and receive a low dose. Based on current knowledge of relative biological effectiveness, the efficacy of proton therapy on the tumor compared to photon therapy can be considered equivalent with lower levels of uncertainty. In the present study, the impact of photon irradiation versus proton irradiation on neurocognition will now be directly compared. A bicentric, randomized study will investigate whether treating patients with WHO Grade 2 and 3 gliomas with proton radiation results in a different temporal course of neurocognitive function after treatment compared to photon radiation therapy.

This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with malignant glioma . Autologous TILs are expanded from tumor resections and infused i.v. into the patient after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07799933) administered as a single agent and in combination with other study medicines in people with solid tumors. This study is seeking participants who have an advanced solid tumor with a certain type of abnormal gene called "BRAF" and available treatments are no longer effective in controlling their cancer. All participants in this study will receive PF-07799933. PF-07799933 comes as a tablet to take by mouth, 2 times a day. Depending on the part of the study, participants may also receive another study medicine: * People with melanoma or other solid tumors may also receive binimetinib. Binimetinib comes as a tablet to take by mouth, 2 times a day. * People with colorectal cancer may also receive cetuximab or cetuximab and mFOLFOX6 (Chemotherapy regimen). Cetuximab will be given weekly (or every two weeks) in the clinic as a shot given in the vein or port (intravenous, IV). Participants may receive the study medicines for about 2 years. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

This is a pilot clinical trial determining the effect of a Methionine-reduced diet on serum levels in subjects with solid tumors. These are subjects who will receive systemic standard of care cancer therapy.

This is an open-label, multicenter dose-escalation study to be followed by a dose expansion to define the optimal dose of GLIX1 as monotherapy by reviewing safety and tolerability, disease characteristics and pharmacokinetic profiles and preliminary clinical activity in participants with a high grade diffuse glioma that progressed during or recurred after prior standard of care therapies or investigational therapies as clinically indicated. Patients will be treated daily with GLIX1 capsules until disease progression or unacceptable safety.

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.

The goal of this clinical research study is to learn about the safety and effects of M032 given directly into the tumor in children and adults with DMG and who have received standard-of-care radiation therapy.

This is a prospective, multicenter, single-arm, pilot clinical investigation, aimed at evaluating the safety and preliminary efficacy of the GlioHook implant in patients with high-grade glioma undergoing surgical resection followed by standard of care (SoC) treatment. GlioHook is a sterile medical device designed to be implanted after tumour resection surgery in suspected high grade glioma patients, covering the entire surface of the tumour resection margins, decreasing infiltration and focalizing the disease, while improving the effects of radiotherapy. Once implanted, GlioHook exerts a dual mechanism that combines tumour cell focalization and radiosensitization.

This multicenter observational cohort study aims to develop and validate an artificial intelligence (AI)-assisted diagnostic system for preoperative molecular subtyping of pediatric brain tumors using routine magnetic resonance imaging (MRI). The study will include seven major pediatric brain tumor categories: glioma, medulloblastoma, ependymoma, atypical teratoid/rhabdoid tumor (AT/RT), intracranial germ cell tumors, craniopharyngioma, and choroid plexus tumors. The study includes a retrospective cohort for model development and internal/external validation, and a prospective cohort for further validation. Retrospective data will be collected from pediatric patients who underwent first surgical treatment between January 1, 2020 and December 31, 2025. Prospective enrollment will begin on July 15, 2026, with an anticipated sample size of 150 participants. The AI system will analyze preoperative MRI sequences, including T1-weighted, contrast-enhanced T1-weighted, T2-weighted, and FLAIR images, to predict key molecular markers and integrated diagnostic categories. The primary objective is to evaluate the diagnostic performance of the AI system for prespecified molecular prediction tasks using postoperative histopathology and molecular testing as the reference standard. Secondary objectives include assessing agreement with integrated diagnosis, comparing performance against blinded radiologists, and exploring prognostic associations of AI-predicted subgroups.

This study will test the safety and effectiveness of a combination of pembrolizumab, olaparib, and temozolomide to see how well these drugs work when given together in people with a glioma that either did not respond to previous treatment or came back after treatment.

This is an interventional neuroimaging study that will examine whether fMRI neurofeedback can shift language network activity away from regions affected by glioma prior to surgery.

Brain tumor surgery in so-called "eloquent" brain areas aims to remove as much tumor as possible while preserving neurological functions. Standard surgical planning typically focuses on discrete, anatomically defined cortical regions. However, modern neuroscience demonstrates that most brain functions arise from distributed networks of interconnected areas rather than isolated spots - a concept that standard navigation tools do not fully capture. The CORTEX study evaluates a surgical workflow - termed "connectome-guided network-based navigation" - in which advanced diffusion MRI processing is used to reconstruct patient-specific maps of white matter pathways and large-scale brain networks. These maps are imported into a clinical neuronavigation system to guide preoperative planning and intraoperative decision-making for patients with gliomas or brain metastases in eloquent regions. The primary aims are to determine how often network-based information leads to meaningful changes in surgical strategy compared with conventional anatomy-based planning, and to assess early neurological outcomes. Secondary objectives include characterizing the extent of tumor removal, the proximity of the resection to critical white matter tracts, and the feasibility of implementing this pipeline in a high-volume clinical setting.