Clinical Research Directory

A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM. All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (\*).

Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma

This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma

This is an open label study to determine the safety and preliminary evidence of a therapeutic effect of azeliragon in patients with newly diagnosed glioblastoma receiving concurrent radiation and temozolomide.

Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care

This is a Phase 3 prospective, randomized, superiority, open-label, multi-site study. The overview of this study is as follows: * A Screening/Baseline Period of 21 days. During this time, patients will be randomized into a 1:2 allocation of Arm A:Arm B. * A Perioperative/Operative Phase where patients will undergo tumor resection (Arm A) or tumor resection plus GammaTile implantation (Arm B). * An EBRT Prior to Start Period. This occurs within 10 business days prior to EBRT and Concurrent TMZ Phase. * An EBRT and Concurrent TMZ Phase, which will begin 30 ±10 days post-surgery. EBRT (30 fractions) and TMZ will be administered up to 5 days a week for 6 weeks in Arm A, and EBRT (20 fractions) and TMZ will be administered for up to 5 days a week for 4 weeks in Arm B. TMZ will be administered at a dose of 75 mg/m2/day orally for each Arm. * An Adjuvant TMZ Phase, which begins 28 ±7 days following the EBRT and Concurrent TMZ Phase, and is comprised of six 28-day cycles. TMZ (150-200 mg/m2/day orally) will be administered for the first 5 days of each 28-day cycle for each Arm. Tumor treating fields are allowed but are not mandated during this phase. Up to 6 additional cycles (for a total of 12) can be completed at the discretion of the Investigator. * An Early Discontinuation/Follow-Up Phase will occur 28 ±7 days after completion of Cycle 6 of the Adjuvant TMZ Phase, regardless of the total number of cycles completed or any delays in cycle start. If fewer than six cycles are completed, the first follow-up assessment will occur 28 ±7 days after the last administered dose of adjuvant TMZ. If patient has a qualifying event requiring entrance to Early Discontinuation Phase, the first follow-up assessment will occur as soon as feasible, but within 28 days. For any unscheduled visits, data collected should be documented in the case report form (CRF) and must include, but are not limited to, safety evaluations, survival status, and disease status.

A Phase 2b Clinical Study With a Combination Immunotherapy in Newly Diagnosed Patients With Glioblastoma

The purpose of this study is to assess progression-free survival (PFS) and overall survival (OS) in newly diagnosed Glioblastoma (GBM) participants treated with IGV-001 as compared with placebo.

Personalized Radiation Therapy for GBM

The study is a pilot study to estimate the efficacy of personalized dose-escalation radiation therapy in patients with glioblastoma, as measured by estimating the median of progression-free survival. Toxicity, patterns of recurrence, and overall median survival will be measured as secondary endpoints. Adverse events will be monitored.

ctDNA-Guided Intraventricular Therapy for CNS Malignancies

This prospective, single-center study will evaluate whether cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) testing using the Belay Summit assay can improve the clinical management of patients with malignant gliomas or brain metastases from non-small cell lung cancer (NSCLC) or breast cancer who are suspected of having central nervous system (CNS) disease. Patients undergoing clinically indicated CSF evaluation will receive standard clinical testing, including CSF cytology and the Belay Summit ctDNA assay. Treatment decisions will remain at the discretion of the treating multidisciplinary neuro-oncology team. The primary objective is to evaluate 6-month clinical CNS progression-free survival (cCNS-PFS), with secondary objectives assessing safety and the association between CSF ctDNA dynamics and clinical outcomes. Exploratory proteogenomic analyses will be performed on residual CSF specimens when sufficient sample is available.

A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Standard of Care and in Recurrent Glioblastoma as a Single Agent.

A Dose Finding Study of \[177Lu\]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination with Standard of Care and in Recurrent Glioblastoma as a Single Agent

Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations

This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that has spread from where it first started (primary site) to other places in the body (metastatic) and that does not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Pediatric Long-Term Follow-up and Rollover Study

A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.

PH Weighted Chemical Exchange Saturation Transfer MRI-Based Surgical Resection to Improve Survival in Patients With Glioblastoma

This phase III trial compares pH weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI)-based surgical resections to standard of care surgical resections for the treatment of patients with glioblastoma. Standard of care therapy for glioblastoma is surgery to remove tumor tissue that enhances on standard MRI imaging, however, it has been shown that significant tumor burden exists in the region around the tumor tissue that does not enhance with standard MRI. MRI is a procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and tumor tissue. CEST MRI is a technique that uses differences in the tissue environment, like protein concentration or intracellular pH, to generate contrast differences. CEST MRI may identify tumor tissue that does not enhance with standard of care MRI. PH weighted CEST MRI based surgical resection may be more effective compared to standard of care surgical resection in treating patients with glioblastoma.

Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM

The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. The development of effective treatments against glioblastoma is thus limited due to the BBB that prevents most drugs injected in the bloodstream from getting into brain tissue where the tumour is seated. The SonoCloud-9 (SC9) is an investigational device using ultrasound technology and specially developed to open the BBB in the area of and surrounding the tumour. The transient opening of the BBB allows more drugs to reach the brain tumour tissue. Carboplatin is a chemotherapy that is approved to treat different cancer types alone or in combination with other drugs, and has been used in the treatment of glioblastoma. Despite its proven efficacy in the laboratory on glioblastoma cells, carboplatin does not readily cross the BBB in humans. A clinical trial has shown that in combination with the SonoCloud-9, more carboplatin can reach the brain tumour tissue. The objective of the proposed trial is to show that the association - carboplatin with the SonoCloud-9 - will increase efficacy of the drug in patients with recurrent glioblastoma.

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).

A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma

The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma multiforme (GBM). The main question it aims to answer is: Does niraparib improve overall survival (OS) compared to TMZ? Participants will be randomly assigned to one of two treatment arms: niraparib or TMZ. * study drug (Niraparib) or * comparator drug (Temozolomide - which is the standard approved treatment for MGMT unmethylated glioblastoma). The study medication will be taken daily while receiving standard of care radiation therapy (RT) for 6-7 weeks. Participants may continue to take the niraparib or TMZ adjuvantly as long as the cancer does not get worse or completion of 6 cycles of treatment (TMZ). A total of 450 participants will be enrolled in the study. Participants' tasks will include: * Complete study visits as scheduled * Complete a diary to record study medication

Study to Evaluate the Safety, Tolerability, Immunogenicity and Preliminary Efficacy of ITI-1001 In Patients With Newly Diagnosed Glioblastoma (GBM)

This Phase I clinical trial will evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of 8 mg ITI-1001 in participants with newly diagnosed glioblastoma (GBM).

Assessment of a Large US EHR Database as Meeting FDA Fit-for-Purpose Requirements to Provide External Controls for Study BPM31510 in Participants With Glioblastoma

Glioblastoma is a rare, aggressive brain tumor that leads to death within 2 years of diagnosis in more than half of patients. There are currently 123 studies ongoing that are testing treatments for glioblastoma. BPGbio has developed BPM31510 and is executing an ongoing single-arm Phase 2 study (NCT04752813) targeting 50 participants. Because glioblastoma is a rare and often fatal disease with multiple drugs in development, a randomized placebo-controlled trial is unlikely to be feasible. Therefore, BPGbio is exploring the possible use of untreated patients from the Truveta database to create a control group. The purpose of this study is to explore whether the Truveta database in this indication meets FDA criteria as fit-for-purpose for regulatory use.

Magnetic Resonance Fingerprinting Guided Extended Resection in Glioblastomas

Magnetic resonance imaging, MRI, is a procedure that uses radio waves, a powerful magnet, and a computer to make a series of detailed pictures of areas inside the body. The goal of this study is to determine if MR fingerprinting, new way of acquiring MRI images, can help identify the extent of tumor spread in the brain, better than routine MRI images.

N-803 and PD-L1 t-haNK Combined With Bevacizumab for Recurrent or Progressive Glioblastoma

This study consists of 2 portions. The phase 2 portion is an open-label, single-arm study to evaluate the safety and efficacy of NAI, PD-L1 t-haNK, and bevacizumab combination therapy in participants with recurrent or progressive GBM. The phase 2B portion is an open-label, randomized study to evaluate the efficacy and safety for the following 2 experimental arms in participants with recurrent or progressive GBM: NAI, bevacizumab, and TTFields combination therapy (Arm A) or NAI, PD-L1 t-haNK, bevacizumab, and TTFields combination therapy (Arm B). Phase 2 Treatment for all enrolled participants will consist of repeated cycles of 28 days for a maximum treatment period of 76 weeks (19 cycles) as follows: Every 2 weeks (Days 1 and 15 of a 28-day cycle) Fourteen (14) participants were enrolled in the phase 2 portion of this study as of the date of this v02 protocol. No additional participants will be administered therapy in phase 2. Phase 2B Participants will be randomized 1:1 to 1 of 2 experimental arms (Arm A or Arm B). Treatment for all enrolled participants will consist of repeated 8-week cycles for a maximum treatment period of up to 80 weeks (10 cycles). Experimental Arm (A): Every 2 weeks (Days 1, 15, 29, and 43 of an 8-week cycle) Up to twenty (20) participants will be randomized in phase 2B (up to 10 participants/arm. Duration of Treatment: Participants will receive study treatment for up to 76 weeks during phase 2 (up to 19 repeated 28-day cycles) and for up to 80 weeks (up to 10 repeated 8-week cycles) during phase 2B or until they report unacceptable toxicity (not corrected with dose reduction), withdraw consent, or if the Investigator feels it is no longer in the participant's best interest to continue treatment. Treatment may also be discontinued if the participant has confirmed PD per iRANO, unless the participant is clinically stable and is considered potentially deriving benefit per Investigator's assessment. Duration of Follow-up: Participants who discontinue study treatment should remain in the study for follow-up. Participants should be followed for collection of survival status, posttreatment therapies (phase 2 and phase 2B), and medical history (phase 2B only) every 12 weeks (± 2 weeks) for the first 2 years then yearly thereafter for an additional 3 years. The maximum duration of follow-up is 5 years (260 weeks).

Pilot Study Evaluating Panitumumab-IRDye800 as an Optical Imaging Agent to Detect Intracranial Lesions During Neurosurgical Procedures

This pilot clinical study evaluates the safety and imaging performance of panitumumab-IRDye800 (pan800), a fluorescent, EGFR-targeted imaging agent - in patients undergoing neurosurgical resection of intracranial lesions.

Tofacitinib in Recurrent GBM Patients

The purpose of this study is to examine the effects of Tofacitinib in patients with recurrent Glioblastoma.

Vortioxetine for Newly Diagnosed Glioblastoma

There is a very urgent need to improve on the currently limited treatment options for patients with glioblastoma. Despite extensive knowledge on the molecular pathogenesis of glioblastoma obtained through genomic, transcriptional and proteomic profiling, targeted therapy efforts have not yielded major advances, likely because of interindividual and intraindividual tumor heterogeneity and redundant oncogenic pathway activation. Accordingly, there is a strong rationale to approach the challenge of glioblastoma from a different angle, e.g., by ex vivo drug sensitivity profiling which is agnostic to the molecular profile of a tumor. This approach that we have termed "pharmacoscopy", has previously been explored in liquid cancers and probably led to improved patient outcomes. Using pharmacoscopy, the antidepressant drug, vortioxetine, has been identified as a lead candidate for further exploration in patients with glioblastoma. Vortioxetine also demonstrated synergistic anti-glioma activity in combination with temozolomide or lomustine. The ReVoGlio trial aims at demonstrating that vortioxetine, a drug selected based on ex vivo drug profiling (pharmacoscopy), is of benefit for patients with newly diagnosed glioblastoma.

Phase I Trial of DNA-PK Inhibitor (PEPOSERTIB ) in Combination With Radiation and Adjuvant Temozolomide in Newly Diagnosed MGMT Unmethylated and Recurrent Glioblastoma

This phase I trial investigates the side effects and best dose of Peposertib, and to see how well it works in combination with radiation therapy in treating patients with newly diagnosed MGMT unmethylated glioblastoma or gliosarcoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Peposertib may further stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Peposertib with radiation therapy may work better than radiation therapy alone in treating patients with glioblastoma or gliosarcoma.

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.

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.