Clinical Research Directory

Dabrafenib and/or Trametinib Rollover Study

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.

Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors

This clinical trial tests how well entrectinib works to treat patients less than 3 years of age with NTRK 1/2/3 or ROS1 fused, high grade glioma or other central nervous system (CNS) tumors.

A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM)

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

Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)

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.

Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype

Background: Gliomas are the most common malignant brain tumors. Some have certain changes (mutations) in the genes isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2). If there are a high number of mutations in a tumor, it is called hypermutator phenotype (HMP). The drug nivolumab helps the immune system fight cancer. Researchers think it can be more effective in patients with IDH1 or IDH2 mutated gliomas with HMP. They will test gliomas with and without HMP. Objectives: To see if nivolumab stops tumor growth and prolongs the time that the tumor is controlled. Eligibility: Adults 18 years or older with IDH1 or IDH2 mutated gliomas Design: Participants will be screened with: Medical history Physical exam Heart, blood, and pregnancy tests Review of symptoms and activity levels Brain magnetic resonance imaging (MRI). Participants will lie in a cylinder that takes pictures in a strong magnetic field. Tumor samples Participants will get the study drug in 4-week cycles. They will get it through a small plastic tube in a vein (intravenous \[IV\]) on days 1 and 15 of cycles 1-4. For cycles 5-16, they will get it just on day 1. On days 1 and 15 of each cycle, participants will repeat some or all screening tests. After cycle 16, participants will have 3 follow-up visits over 100 days. They will answer health questions, have physical and neurological exams, and have blood tests. They may have a brain MRI. Participants whose disease did not get worse but who finished the study drug within 1 year of treatment may have imaging studies every 8 weeks for up to 1 year. Participants will be called or emailed every 6 months with questions about their health.

A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (rHGG) and Newly Diagnosed Glioblastoma (nGBM) Participants With EGFR Alterations or Fusions

This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma (HGG) and newly-diagnosed glioblastoma (nGBM). BDTX-1535 was designed to block a growth signal important to some cancers. BDTX-1535 is being tested in this study to see if it can be given safely to people who have tumors that can be dependent on that growth signal because of changes in a protein called EGFR. These gene changes are called amplifications, mutations, fusions or alterations and are found only in the tumors. The study design includes a Phase 0 component with PK/PD-trigger for participant enrollment into an Expansion Phase 1 component. The primary objective of the Phase 0 component is to evaluate the PK endpoints of BDTX-1535. The primary objective of the Phase 1 component is to establish the safe dose of BDTX-1535 to be used in participants with a specified treatment regimen, three of which include standard of care radiotherapy for nGBM participants.

Novel Indenoisoquinolone CMYC/TOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma

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.

Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy

Background: Glioma is a type of brain cancer. Some of these tumors have gene mutations. These mutations can cause a substance called 2-HG to build up in the brain. This makes the tumors more aggressive. Researchers want to better understand 2-HG buildup in the brain. They hope this can help them design better ways to test for gliomas. Objective: To monitor the level of 2-HG in the brains of people with gliomas that have mutations in the IDH1 or IDH2 genes. Eligibility: People ages 18 and older with gliomas with mutations in the IDH1 or IDH2 genes Design: Participants will be screened with: Medical and cancer history Physical exam Reviews of their symptoms and ability to perform normal activities Blood and urine tests MRI scan Samples of their tumor from a past surgery Documentation of their diagnosis and mutation status Participants will have an initial evaluation. This will include repeats of screening tests. It will also include: Neurological exam MRS and MRI scans of the brain: Participants will lie on a table that slides into a metal cylinder. A coil or soft padding will be placed around their head. They will have a contrast agent injected into a vein. Pictures will be taken of the brain. Participants will have follow-up visits every 2-6 month for the rest of their life. Visits will include scans.

Metronomic Temozolomide With Dexbrompheniramine for Recurrent High-Grade Glioma/Glioblastoma

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.

GD2-CAR T Cells for Pediatric Brain Tumours

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.

A Study of the Safety, Dosing, and Delivery of NEO100 in Patients With Pediatric Brain Tumors

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).

Study of Relatlimab and Nivolumab (Opdualag) in Replication Repair Deficient HGG and DIPG

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

Targeted Pediatric High-Grade Glioma Therapy

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.

Study of Olutasidenib and Temozolomide in HGG

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.

A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors

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.

PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma

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

Multiparametic Metabolic and Hypoxic PET/MRI for Disease Assessment in High Grade Glioma

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.

Glioma Supra Marginal Incision Trial

G-SUMIT is a pilot, phase II,randomized controlled trial to evaluate the feasibility of performing a large-scale trial in patients undergoing surgery for first-time diagnosis of high grade glioma (HGG) in a surgically favorable anatomical location to answer the following: Does extending the margin of resection 1 cm beyond visible enhanced volume on MRI result in (a) an increase in overall survival? (b) result in a similar rate of "clinically-significant" neurological worsening during 30 days post surgery and quality of life at 6 and 12 months?

MRI in High-Grade Glioma Patients Undergoing Chemoradiation

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.

Expedited Laser Interstitial Thermal Therapy + Chemoradiation For Newly Diagnosed High Grade Gliomas

The investigators of this study want to see if shortening the total treatment time for brain tumors is safe.The treatment for participant's brain tumors is laser surgery (Laser Interstitial Thermal Therapy (LITT)) followed by radiation with chemotherapy. For participants, the total time of treatment from surgery to the end of radiation and chemotherapy is about l 0 weeks long. This study asks whether it is safe to shorten the total treatment to 7 weeks. To shorten the total treatment time, investigators want to see if it is safe to start radiation with chemotherapy within 5 days after surgery. Usually patients start their radiation with chemotherapy about 21-28 days after the surgery. Shortening the total time of treatment may allow investigators to kill the cancer cells more effectively.

Prospective Surgical Study on the Pattern of Electrical Activity in High Grade Glioma as a Predictor of Progression

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.

C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)

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.

Study of DSP-0390 in Patients With Recurrent High-Grade Glioma

This is a study of DSP-0390 in patients with recurrent high grade glioma.

Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors

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)