Clinical Research Directory

Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant

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.

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.

DB107-Retroviral Replicating Vector (RRV) Combined With DB107-Flucytosine (FC) in Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma

The purpose of this study is to determine if the investigational products, DB107-RRV and DB107-FC, as a combination treatment will shrink high-grade glioma (HGG) in patients with recurrent/progressive, resectable or unresectable disease and increase the time that disease is controlled.

Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors

The goal of this clinical trial is to learn if intratumoral administration of DNX-2401 works to treat recurrent and refractory high grade brain tumors in children and young adults. It will also learn about the safety of DNX-2401. The main questions it aims to answer are: * Does a single intratumoral administration of DNX-2401 elicit tumor response and improve survival? * Is a single intratumoral administration of DNX-2401 safe and well tolerated? Participants will: * Undergo surgery for tumor biopsy followed by a single intratumoral administration of DNX-2401 * Visit the clinic periodically for checkups and tests

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.

Study of Sonodynamic Therapy in Participants With Recurrent High-Grade Glioma

A Phase 0 single center, first in human, open-label study of ascending energy doses of sonodynamic therapy (SDT) utilizing the MRgFUS combined with intravenous ALA to assess safety and efficacy in up to 45 participants with recurrent HGG. Eligible participants who are scheduled for resection will be administered intravenous (IV) aminolevulinic acid HCl (ALA) approximately six to seven (6-7) hours prior to receiving sonodynamic therapy (SDT).

Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG

This is a single-center, open-label, dose-escalating Phase 0 trial that will enroll participants with a confirmed diagnosed recurrent high-grade glioma (grade 3 or 4 per WHO criteria) targeting the mTOR pathway. Eligible participants will be administered a single infusion of temsirolimus through super-selective intra-arterial infusion or intravenous infusion. Participants will receive the study drug administration on the same day as the planned surgical resection of the tumor.

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.

Window Trial of Fluorescently Labeled Nivolumab-IRDye800 (Nivo800) in High Grade Glioma (HGG)

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.

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

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.

Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors. Primary objectives * To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). Secondary objectives * To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). * To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).

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.

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

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.

Trametinib and Everolimus for Treatment of Pediatric and Young Adult Patients With Recurrent Gliomas (PNOC021)

This phase I trial studies the side effects and best dose of trametinib and everolimus in treating pediatric and young adult patients with gliomas that have come back (recurrent). Trametinib acts by targeting a protein in cells called MEK and disrupting tumor growth. Everolimus is a drug that may block another pathway in tumor cells that can help tumors grow. Giving trametinib and everolimus may work better to treat low and high grade gliomas compared to trametinib or everolimus alone.

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)

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.

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.

A Phase 1b Study of PTC596 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma and High Grade Glioma

The goal of this study is to evaluate the safety of the study drug PTC596 (Unesbulin) taken in combination with radiotherapy (RT) when given to pediatric patients newly diagnosed with High-Grade Glioma (HGG) including diffuse intrinsic pontine glioma (DIPG). The main aims of the study are to: * Find the safe dose of the study drug PTC596that can be given without causing serious side effects. * Find out the amount of drug that enters blood (in all patients) and tumor (in patients who receive drug prior to a planned surgery for removal of their brain tumor) During the first cycle (6-7weeks), patients will receive drug orally twice a week in combination with daily RT. During subsequent cycles (4 weeks each), they will receive only the study drug orally twice a week. Funding Source - FDA OOPD

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, lumbar puncture, and blood tests might help investigators predict who might have larger changes in their brain function after radiation.

A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion

This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given. The study will also evaluate the safety of larotrectinib when given with chemotherapy in your children; as well as the safety larotrectinib when given post-focal radiation therapy.

Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion

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.

DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma

This is a multicenter, open-label study of DB107-RRV (formerly Toca 511) and DB107-FC (formerly Toca FC) when administered following surgical resection in newly diagnosed High Grade Glioma (HGG) patients. The study is designed to evaluate whether treatment with DB107-RRV in combination with DB107-FC when added to standard of care provides clinical benefit to newly diagnosed HGG when compared to historical performance previously determined in well controlled clinical trials published in the peer reviewed literature. This study is going to be conducted in newly diagnosed HGG patients receiving with maximum surgical resection treatment followed by radiation and temozolomide treatment using the established Stupp Protocol for O6-methylguanine-DNA methyl-transferase (MGMT) methylated patients or radiation therapy for MGMT unmethylated patients.