A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (GBM AGILE)

June 1, 2026 updated by: Global Coalition for Adaptive Research

GBM AGILE: Global Adaptive Trial Master Protocol: An International, Seamless Phase II/III Response Adaptive Randomization Platform Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent GBM

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 (*).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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. Its goals are to identify effective therapies for glioblastoma and match effective therapies with patient subtypes. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to Arms based on their performance. The primary endpoint is overall survival (OS).

GBM AGILE is designed to efficiently evaluate therapies. The trial will be conducted under a single Master Investigational New Drug Application/Clinical Trial Application and Master Protocol, allowing multiple drugs and drug combinations from different pharmaceutical companies to be evaluated simultaneously. The plan is to add experimental therapies as new information about promising new drugs are identified and remove therapies as they complete their evaluation.

Study Type

Interventional

Enrollment (Estimated)

2250

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • St Leonards, New South Wales, Australia, 2065
        • Recruiting
        • Northern Sydney Cancer Centre/Royal North Shore Hospital
        • Principal Investigator:
          • Helen Wheeler, MD
        • Contact:
      • Waratah, New South Wales, Australia, 2298
        • Recruiting
        • Calvary Mater Newcastle
        • Contact:
        • Principal Investigator:
          • Faisal Hayat, MD
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Recruiting
        • Royal Brisbane and Women's Hospital
        • Principal Investigator:
          • Zarnie Lwin, MD
        • Contact:
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Recruiting
        • Austin Health
        • Principal Investigator:
          • Hui Gan, MBBS, FRACP, PhD
        • Contact:
      • Melbourne, Victoria, Australia
        • Recruiting
        • Peter MacCallum Cancer Centre
        • Principal Investigator:
          • Mark Rosenthal, Prof.
        • Principal Investigator:
          • Jim Whittle, MD
        • Contact:
        • Contact:
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • James Perry, MD, FRCPC
      • Toronto, Ontario, Canada, M5G 2C1
        • Recruiting
        • Princess Margaret Cancer Centre
        • Principal Investigator:
          • Warren Mason, MD
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Recruiting
        • Montreal Neurological Institute and Hospital, McGill University
        • Principal Investigator:
          • Scott Owen, MD
        • Contact:
      • Sherbrooke, Quebec, Canada, J1H 5H3
        • Active, not recruiting
        • Universite de Sherbrooke
  • France
      • Bron, France, 69677
        • Recruiting
        • Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
        • Principal Investigator:
          • Francois Ducray, MD
        • Contact:
      • Marseille, France, 13005
        • Recruiting
        • Hopital de la Timone
        • Contact:
        • Principal Investigator:
          • Emelie Tabouret, MD
      • Paris, France, 75013
        • Recruiting
        • Hopital Piti-Salpetriere
        • Contact:
        • Principal Investigator:
          • Mehdi Touat, MD
  • Germany
      • Cologne, Germany, 50937
        • Active, not recruiting
        • Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
      • Frankfurt, Germany, 60528
        • Recruiting
        • Dr. Senckenbergisches Institut für Neuroonkologie
        • Contact:
        • Principal Investigator:
          • Michael Ronellenfitsch, MD, PhD
      • Heidelberg, Germany, 69120
        • Recruiting
        • Universitätsklinik Heidelberg
        • Principal Investigator:
          • Antje Wick, MD
        • Contact:
      • Mannheim, Germany, 68167
        • Recruiting
        • Universitaetsklinikum Heidelberg - Neurologische Klinik
        • Principal Investigator:
          • Michael Platten, MD
        • Contact:
      • Regensburg, Germany, 93053
        • Recruiting
        • Universitätsklinikum Regensburg
        • Principal Investigator:
          • Peter Hau, MD
        • Contact:
      • Tübingen, Germany, 72076
        • Recruiting
        • Universitatsklinikum Tubingen
        • Principal Investigator:
          • Ghazaleh Tabatabai, MD
        • Contact:
  • Switzerland
      • Zurich, Switzerland
        • Recruiting
        • University Hospital Zurich
        • Principal Investigator:
          • Michael Weller, MD
        • Contact:
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Switzerland, 1011
        • Recruiting
        • Centre Hospitalier Universitaire Vaudois Lausanne
        • Principal Investigator:
          • Andreas Hottinger, MD
        • Contact:
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • Recruiting
        • University of Alabama at Birmingham
        • Principal Investigator:
          • Louis B Nabors, MD
        • Contact:
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • University of California, San Diego
        • Principal Investigator:
          • David Piccioni, MD, PhD
        • Contact:
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles
        • Contact:
        • Principal Investigator:
          • Phioanh Nghiemphu, MD
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
        • Contact:
        • Principal Investigator:
          • Jethro Hu, MD
      • Orange, California, United States, 92868
        • Recruiting
        • St. Joseph Hospital
        • Principal Investigator:
          • Lars Anker, MD
        • Contact:
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Principal Investigator:
          • Nicholas Butowski, MD
        • Contact:
      • Stanford, California, United States, 94305
        • Completed
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Denver
        • Principal Investigator:
          • Denise Damek, MD
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Recruiting
        • Yale Cancer Center / Smilow Cancer Hospital*
        • Contact:
        • Principal Investigator:
          • Nicholas Blondin, MD
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Completed
        • Mayo Clinic Cancer Center
      • Miami, Florida, United States, 33136
        • Recruiting
        • Sylvester Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Macarena I De La Fuente, MD
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Contact:
        • Principal Investigator:
          • Patrick Grogan, MD
    • Georgia
      • Atlanta, Georgia, United States, 30309
      • Atlanta, Georgia, United States, 30322
        • Completed
        • Winship Cancer Institute of Emory University
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Active, not recruiting
        • LSU Health Sciences Center - New Orleans
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Patrick Wen, MD
        • Contact:
        • Contact:
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Dana Farber Cancer Institute
        • Contact:
        • Principal Investigator:
          • Patrick Wen, MD
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Active, not recruiting
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Recruiting
        • Allina Health Systems/Abbott Northwestern Hospital
        • Principal Investigator:
          • Andrea Wasilewski, MD
        • Contact:
      • Rochester, Minnesota, United States, 55905
        • Completed
        • Mayo Clinic Cancer Center - Rochester
    • Mississippi
      • Jackson, Mississippi, United States, 39213
        • Completed
        • University of Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Completed
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
        • Principal Investigator:
          • Lyndon Kim, MD
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Principal Investigator:
          • Andrew Lassman, MD
        • Contact:
      • New York, New York, United States, 10016
        • Recruiting
        • Perlmutter Cancer Center, NYU Langone Health
        • Principal Investigator:
          • Jonathan Yang, MD, PhD
        • Contact:
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center*
        • Principal Investigator:
          • Ingo Mellinghoff, MD
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Contact:
        • Principal Investigator:
          • Katherine Peters, MD, PhD
      • Winston-Salem, North Carolina, United States, 272157
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Mina Lobbous, MD
        • Contact:
      • Cleveland, Ohio, United States, 44106
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Cancer Center
        • Contact:
        • Principal Investigator:
          • Pierre Giglio, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania - Perelman Center for Advanced Medicine
        • Principal Investigator:
          • Arati Desai, MD
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15212
        • Active, not recruiting
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Medical Center - Hillman Cancer Center
        • Principal Investigator:
          • Jan Drappatz, MD
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina - Hollings Cancer Center
        • Contact:
        • Principal Investigator:
          • Scott Lindhorst, MD
    • Texas
      • Austin, Texas, United States, 78705
        • Active, not recruiting
        • Texas Oncology - Austin
      • Dallas, Texas, United States, 75390
        • Active, not recruiting
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas - MD Anderson Cancer Center
        • Principal Investigator:
          • Shiao-Pei Weathers, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah - Huntsman Cancer Institute
        • Principal Investigator:
          • Howard Colman, MD, PhD
        • Contact:
        • Contact:
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Health
        • Contact:
        • Principal Investigator:
          • David Schiff, MD
    • Washington
      • Seattle, Washington, United States, 98101
        • Active, not recruiting
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Active, not recruiting
        • Froedtert Hospital/Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Newly Diagnosed Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
  • Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
  • Availability of tumor tissue representative of GBM from definitive surgery or biopsy.

Recurrent Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
  • Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
  • Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
  • Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
  • Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.

Newly Diagnosed Exclusion Criteria:

  • Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
  • Extensive leptomeningeal disease.
  • QTc > 470 msec
  • History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Recurrent Exclusion Criteria:

  • Early disease progression prior to 3 months (12 weeks) from the completion of RT.
  • More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
  • Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
  • Any prior treatment with prolifeprospan 20 with carmustine wafer.
  • Any prior treatment with an intracerebral agent.
  • Receiving additional, concurrent, active therapy for GBM outside of the trial
  • Extensive leptomeningeal disease.
  • QTc > 470 msec
  • History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control Arm

Newly Diagnosed GBM: Radiation therapy (XRT) 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation, and the start of the first cycle of Maintenance Therapy 2-6 weeks after the last day of radiotherapy. The start of all subsequent maintenance therapy cycles (2-12) every 4 weeks + 7 days after the first daily dose of temozolomide of the preceding cycle. Total number of cycles should comply with institutional or country standards. During maintenance therapy, the first cycle of temozolomide will be at 150 mg/m2 for Days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for Days 1-5 of a 28-day cycle.

Recurrent GBM: Lomustine started at 110 mg/m2/day on Day 1 of a 42-day cycle as per local standards. Treatment will continue for up to 6 total cycles.
Drug: Temozolomide
Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg
Other Names:
  • Temodar
  • Temodal
  • Temcad
Drug: Lomustine
Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg
Other Names:
  • CCNU
  • CeeNU
  • Gleostine
Radiation: Radiation
60 Gy
Experimental: VT1021 Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. Treatment as outlined in section "Experimental: VT1021 Treatment Arm" with the first 6 patients receiving VT1021 at 12 mg/kg twice weekly in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities reported, the dose will be de-escalated to 9 mg/kg two times a week. 6 patients will then be receiving 9 mg/kg two times a week and observed for DLTs for 4 weeks.

Recurrent GBM: Dose Finding Phase is not applicable for patients with Recurrent GBM in the VT1021 treatment arm.
Drug: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Experimental: VT1021 Treatment Arm - Enhanced Safety Management (ESM)

Experimental: VT1021 Treatment Arm - Enhanced Safety Management (ESM) Newly diagnosed MGMT Methylated and Unmethylated GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. PK and PD assessments are done for patients as a part of ESM. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.

Recurrent GBM: ESM is not applicable for patients with Recurrent GBM in the VT1021 treatment arm.
Drug: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Experimental: Troriluzole Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Rolling 6 design. The first 6 patients will receive troriluzole at 100 mg BID for the first two weeks followed by 200 mg BID for the next two weeks in combination with temozolomide and radiation therapy. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 100 mg in the morning and followed by 200 mg in the evening. 6 patients will receive this dose and observed for 4 weeks. If there are two DLTs reported, then this dose will be de-escalated to 100 mg BID. 6 patients will then be receiving this dose and observed for DLTs for 4 weeks.

Recurrent GBM: Rolling 6 design. The first 6 patients receiving troriluzole 100 mg twice a day (BID) for the first two weeks followed by 200 mg BID for the next two weeks in combination with lomustine. The dose de-escalation is similar to that of newly diagnosed patients during the rolling 6 design.
Drug: Troriluzole
Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.
Other Names:
  • BHV-4157
Experimental: Troriluzole Treatment Arm - Enhanced Safety Management (ESM)
Newly diagnosed MGMT Methylated and Unmethylated GBM and Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.
Drug: Troriluzole
Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.
Other Names:
  • BHV-4157
Experimental: VT1021 Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: As confirmed through the dose finding phase) twice weekly during radiation therapy. Rest period: 2-6 weeks from last day of radiation. VT1021 dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with VT1021. After 6 cycles, VT1021 only.

Recurrent GBM: VT1021 (Dosage Form: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: 12mg/kg) twice weekly.
Drug: VT1021

Dosage Form: Infusion for intravenous administration Strength: 10 mg/mL Standard Regimen Newly Diagnosed: Dose as confirmed through the dose finding phase, administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri).

Standard Regimen Recurrent: 12 mg/kg administered twice weekly (Mon and Thurs or Tues and Fri or Mon and Fri). The drug is available as a sterile solution of the acetate salt formulated with phosphate-buffered saline, mannitol, and 2.5% polysorbate 80. The required volume stock solution for the patient is calculated. The corresponding volume is diluted in 500 mL of either 0.9% saline or D5W, prior to intravenous administration.
Experimental: Troriluzole Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily and troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. Rest period: 2-6 weeks from last day of radiation. Troriluzole dosing will continue during the rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with troriluzole. After 6 cycles, troriluzole only.

Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with troriluzole (Dosage Form: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. After 6 cycles, troriluzole only.
Drug: Troriluzole
Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.
Other Names:
  • BHV-4157
Experimental: ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM)

Newly diagnosed MGMT Methylated and Unmethylated GBM: ESM is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.

Recurrent GBM: Supplemental safety assessments including bi-weekly collection of adverse events, dose modification profile, hematology, serum chemistry and coagulation panels. ESM will continue until the Data Safety Monitoring Board (DSMB) suspends collection of additional data.
Biological: ADI-PEG 20
Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week
Other Names:
  • Pegargiminase
Experimental: ADI-PEG 20 Treatment Arm

Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy over 6 weeks. Temozolomide (75 mg/m2 orally daily and ADI-PEG 20 (Dosage Form: Solution for intramuscular injection; Strength: 11.5 ± 1.0 mg/ml; Dose: 36 mg/m2) once a week. Rest period: 2-6 weeks from last day of radiation. ADI-PEG 20 dosing will continue during rest period. Maintenance period: The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Subsequent cycles will be at 200 mg/m2 for days 1-5 of a 28-day cycle. Temozolomide will be administered for up to 6 cycles in the maintenance phase in combination with ADI-PEG 20. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment.

Recurrent GBM: Lomustine 100 mg/m2 orally on day 1 of a 42-day cycle in combination with ADI-PEG 20 (Dosage Form: Solution for IM injection; Strength: 11.5 ± 1.0 mg/ml; Dose: As confirmed by dose finding phase, once a week. After 6 cycles, ADI-PEG 20 only for up to 104 weeks of total treatment.
Biological: ADI-PEG 20
Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week
Other Names:
  • Pegargiminase
Experimental: ADI-PEG 20 Treatment Arm - Dose Finding Phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Dose Finding Phase is not applicable for newly diagnosed patients on the ADI-PEG 20 treatment arm.

Recurrent GBM: Rolling 6 design. The first 6 patients will receive ADI-PEG 20 at 36 mg/m2 once a week in combination with lomustine 100 mg/m2 orally on day 1 of a 42-day cycle. 6 patients will receive this dose and be observed for 4 weeks. If there are two dose limiting toxicities (DLTs) reported, the dose will be de-escalated to 18 mg/m2 once a week. 6 patients will receive this dose and be observed for 4 weeks.
Biological: ADI-PEG 20
Dosage Form: Solution for intramuscular injection Strength: 11.5 ± 1.0 mg/ml Standard Regimen: For newly diagnosed patients, 36mg/m2. For recurrent disease patients, dose as confirmed through the dose finding phase intramuscularly once a week
Other Names:
  • Pegargiminase
Experimental: AZD1390 Treatment Arm
Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks in combination with AZD1390 given on days of radiation followed by 14 days with daily AZD1390. Rest Period 2-4 weeks from the last day of AZD1390. The first cycle of temozolomide will be at 150 mg/m2 for days 1-5 of a 28-day cycle. Second and subsequent cycles of maintenance therapy will be at 200 mg/m2 for days 1-5 of a 28-day cycle, if there is no toxicity. Temozolomide will be administered for up to 6 cycles in the maintenance phase.
Drug: AZD1390
Standard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.
Experimental: Regorafenib Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).

Recurrent GBM: Regorafenib (Dosage Form: Tablet for oral administration; Strength: 40 mg) 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).
Drug: Regorafenib
Dosage Form: Tablet for oral administration Strength: 40 mg Standard Regimen: 160 mg orally (PO) every day (QD) for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)
Other Names:
  • BAY 73-4506
  • Stivarga
Experimental: Paxalisib Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles.

Recurrent GBM: Paxalisib (Dosage Form: Tablet for oral administration; Strength: 15 mg per tablet) 45 mg orally (PO) every day for 21 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 21 days for all subsequent cycles.
Drug: Paxalisib
Dosage Form: Tablet for oral administration Strength: 15 mg Standard Regimen: 45 mg orally (PO) every day for 28 days for the first cycle. If tolerated, increase dose to 60 mg orally (PO) every day for 28 days for all subsequent cycles
Other Names:
  • GDC-0084
Experimental: VAL-083 Treatment Arm- Enrollment concluded

Newly Diagnosed MGMT Methylated and Unmethylated GBM: XRT 60 Gy for 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 4 weeks from the last day of radiation. Maintenance period: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle.

Recurrent GBM: VAL-083 (Dosage Form: Infusion for intravenous administration; Strength: 30 mg/m2) on Day 1, 2 and 3 of 21-day cycle.
Drug: VAL-083
Dosage Form: Infusion for intravenous administration Strength: 40 mg per vial Standard Regimen: 30 mg/m2 on Day 1, 2 and 3 of 21-day cycle. The drug is available in powder form. It is reconstituted with 5 mL of 0.9% Sodium Chloride for Injection, USP. This will produce a solution of 40 mg VAL-083 in 5 mL. The required volume of reconstituted VAL-083 for the patient is then calculated at the rate of 30 mg/m2. The corresponding volume is further diluted into 250 mL of 0.9% Sodium Chloride for Injection, USP, prior to intravenous administration.
Other Names:
  • Dianhydrogalactitol
Experimental: Tinostamustine - Dose finding phase

Newly diagnosed MGMT Methylated and Unmethylated GBM: Tinostamustine Dosage Form: Infusion for intravenous administration; Rolling 6 design. Treatment as outlined in "Investigational: Tinostamustine Treatment Arm" with the first 6 patients receiving Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations. If there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2).

Recurrent GBM: Rolling 6 design. Tinostamustine Dosage Form: Infusion for intravenous administration; Strength: Starting dose 80 mg/m2 on Day 1 of 21-day cycle for up to 12 cycles. The first 6 patients will receive Tinostamustine at 80 mg/m2 over 60 minutes with two potential dose de-escalations if there are two or more dose limiting toxicities at the tested dose, subsequent patients will be enrolled at the next lower dose level (60 mg/m2 and subsequently to 40 mg/m2).
Drug: Tinostamustine
Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.
Other Names:
  • EDO-S101
Experimental: Tinostamustine - Enhanced Safety Management

Newly diagnosed MGMT Methylated and Unmethylated GBM: Treatment as outlined in "Investigational: Tinostamustine Treatment Arm". Dose as determined by the dose finding phase.

Recurrent GBM: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase on Day 1 of 21-day cycle for up to 12 cycles.
Drug: Tinostamustine
Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.
Other Names:
  • EDO-S101
Experimental: Investigation arm: Tinostamustine
Newly diagnosed MGMT Methylated and Unmethylated GBM: XRT total of 60 Gy (2 Gy/fraction) over 6 weeks. Temozolomide 75 mg/m2 orally daily during radiation therapy. Rest Period 2-6 weeks from the last day of radiation. Tinostamustine treatment period: Tinostamustine (Dosage Form: Infusion for intravenous administration; Strength: as determined though the dose finding phase) on Day 1 of 21-day cycle for up to 12 cycles.
Drug: Tinostamustine
Dosage form: Reconstituted powder for intravenous administration Strength: 2mg/mL Standard Regimen: Dose as confirmed through the dose finding phase, on Day 1 of 21-day cycle for up to 12 cycles in the maintenance phase.
Other Names:
  • EDO-S101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Overall survival is defined from the time of randomization to death from any cause. Patients still alive at the time of an analysis will be considered censored at their date of last contact.
From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Progression-free survival is defined as the time from randomization to clinically determined progression or death from any cause. All participants will be included in the analysis of PFS.
From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Tumor Response
Time Frame: From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Tumor response is categorized by Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Response captured from initiation of study treatment until disease progression.
From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Duration of Response (CR + PR)
Time Frame: From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Duration of response (CR+PR) is defined as time from date of response to date of clinically determined disease progression or death from any cause.
From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Global Coalition for Adaptive Research

Collaborators

Bayer
AstraZeneca
Kazia Therapeutics Limited
Biohaven Pharmaceuticals, Inc.
Kintara Therapeutics, Inc.
Vigeo Therapeutics, Inc.
Polaris Group
Knoa Pharma

Investigators

  • Principal Investigator: Tim Cloughesy, MD, GCAR CMO and GBM AGILE Global PI

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2019

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

May 23, 2019

First Submitted That Met QC Criteria

May 30, 2019

First Posted (Actual)

May 31, 2019

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCAR-7213

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Global Coalition for Adaptive Research (GCAR) is in the planning stages at this time.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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