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Et forsøk for å evaluere flere regimer ved nylig diagnostisert og tilbakevendende glioblastom (GBM AGILE)

29. oktober 2026 oppdatert av: Global Coalition for Adaptive Research

GBM AGILE: Global Adaptive Trial Master Protocol: En internasjonal, sømløs fase II/III Response Adaptive Randomization Platform Trial designet for å evaluere flere regimer i nylig diagnostisert og tilbakevendende 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 (*).

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

2250

Fase

  • Fase 2
  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Australia
    • New South Wales
      • St Leonards, New South Wales, Australia, 2065
        • Rekruttering
        • Northern Sydney Cancer Centre/Royal North Shore Hospital
        • Hovedetterforsker:
          • Helen Wheeler, MD
        • Ta kontakt med:
      • Waratah, New South Wales, Australia, 2298
        • Aktiv, ikke rekrutterende
        • Calvary Mater Newcastle
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Rekruttering
        • Royal Brisbane and Women's Hospital
        • Hovedetterforsker:
          • Zarnie Lwin, MD
        • Ta kontakt med:
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
      • Melbourne, Victoria, Australia
        • Rekruttering
        • Peter MacCallum Cancer Centre
        • Hovedetterforsker:
          • Jim Whittle, MD
        • Ta kontakt med:
        • Ta kontakt med:
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
      • Toronto, Ontario, Canada, M5G 2C1
        • Rekruttering
        • Princess Margaret Cancer Centre
        • Hovedetterforsker:
          • Warren Mason, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Aktiv, ikke rekrutterende
        • Montreal Neurological Institute and Hospital, McGill University
      • Sherbrooke, Quebec, Canada, J1H 5H3
        • Aktiv, ikke rekrutterende
        • Université de Sherbrooke
  • Forente stater
    • Alabama
      • Birmingham, Alabama, Forente stater, 35249
        • Rekruttering
        • University of Alabama at Birmingham
        • Hovedetterforsker:
          • Louis B Nabors, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • California
      • La Jolla, California, Forente stater, 92093
      • Los Angeles, California, Forente stater, 90048
        • Aktiv, ikke rekrutterende
        • Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
      • Los Angeles, California, Forente stater, 90095
        • Aktiv, ikke rekrutterende
        • University of California, Los Angeles
      • Orange, California, Forente stater, 92868
        • Rekruttering
        • St. Joseph Hospital
        • Hovedetterforsker:
          • Lars Anker, MD
        • Ta kontakt med:
      • San Francisco, California, Forente stater, 94143
        • Rekruttering
        • University of California, San Francisco
        • Hovedetterforsker:
          • Nicholas Butowski, MD
        • Ta kontakt med:
      • Stanford, California, Forente stater, 94305
        • Fullført
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, Forente stater, 80045
        • Rekruttering
        • University of Colorado Denver
        • Hovedetterforsker:
          • Denise Damek, MD
        • Ta kontakt med:
    • Connecticut
      • New Haven, Connecticut, Forente stater, 06511
        • Rekruttering
        • Yale Cancer Center / Smilow Cancer Hospital*
        • Hovedetterforsker:
          • Nicholas Blondin, MD
        • Ta kontakt med:
    • Florida
      • Jacksonville, Florida, Forente stater, 32224
        • Fullført
        • Mayo Clinic Cancer Center
      • Miami, Florida, Forente stater, 33136
        • Rekruttering
        • Sylvester Comprehensive Cancer Center*
        • Hovedetterforsker:
          • Macarena I De La Fuente, MD
        • Ta kontakt med:
      • Tampa, Florida, Forente stater, 33612
        • Rekruttering
        • Moffitt Cancer Center
        • Hovedetterforsker:
          • Patrick Grogan, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • Georgia
      • Atlanta, Georgia, Forente stater, 30309
        • Aktiv, ikke rekrutterende
        • Piedmont Atlanta Hospital
      • Atlanta, Georgia, Forente stater, 30322
        • Aktiv, ikke rekrutterende
        • Winship Cancer Institute of Emory University
    • Louisiana
      • New Orleans, Louisiana, Forente stater, 70112
        • Fullført
        • LSU Health Sciences Center - New Orleans
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02114
        • Rekruttering
        • Massachusetts General Hospital
        • Hovedetterforsker:
          • Patrick Wen, MD
        • Ta kontakt med:
          • Patrick Wen, MD
          • Telefonnummer: 617-726-5130
          • E-post: pwen@mgb.org
      • Boston, Massachusetts, Forente stater, 02115
    • Michigan
      • Detroit, Michigan, Forente stater, 48202
        • Fullført
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, Forente stater, 55407
        • Rekruttering
        • Allina Health Systems/Abbott Northwestern Hospital
        • Hovedetterforsker:
          • Andrea Wasilewski, MD
        • Ta kontakt med:
      • Rochester, Minnesota, Forente stater, 55905
        • Fullført
        • Mayo Clinic Cancer Center - Rochester
    • Mississippi
      • Jackson, Mississippi, Forente stater, 39213
        • Fullført
        • University of Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, Forente stater, 63110
        • Fullført
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • New York, New York, Forente stater, 10032
        • Rekruttering
        • Columbia University Medical Center
        • Hovedetterforsker:
          • Andrew Lassman, MD
        • Ta kontakt med:
      • New York, New York, Forente stater, 10016
        • Aktiv, ikke rekrutterende
        • Perlmutter Cancer Center, NYU Langone Health
      • New York, New York, Forente stater, 10029
        • Aktiv, ikke rekrutterende
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, Forente stater, 10065
        • Rekruttering
        • Memorial Sloan Kettering Cancer Center*
        • Hovedetterforsker:
          • Ingo Mellinghoff, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • North Carolina
      • Durham, North Carolina, Forente stater, 27710
        • Aktiv, ikke rekrutterende
        • Duke University Medical Center
      • Winston-Salem, North Carolina, Forente stater, 272157
        • Rekruttering
        • Comprehensive Cancer Center of Wake Forest*
        • Hovedetterforsker:
          • Glenn Lesser, MD
        • Ta kontakt med:
    • Ohio
      • Cleveland, Ohio, Forente stater, 44195
        • Rekruttering
        • Cleveland Clinic
        • Hovedetterforsker:
          • Mina Lobbous, MD
        • Ta kontakt med:
        • Ta kontakt med:
      • Cleveland, Ohio, Forente stater, 44106
      • Columbus, Ohio, Forente stater, 43210
        • Aktiv, ikke rekrutterende
        • Ohio State University Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19104
        • Aktiv, ikke rekrutterende
        • University of Pennsylvania - Perelman Center for Advanced Medicine
      • Pittsburgh, Pennsylvania, Forente stater, 15232
        • Aktiv, ikke rekrutterende
        • University of Pittsburgh Medical Center - Hillman Cancer Center
      • Pittsburgh, Pennsylvania, Forente stater, 15212
        • Fullført
        • Allegheny General Hospital
    • South Carolina
      • Charleston, South Carolina, Forente stater, 29425
        • Rekruttering
        • Medical University of South Carolina - Hollings Cancer Center
        • Hovedetterforsker:
          • Scott Lindhorst, MD
        • Ta kontakt med:
    • Texas
      • Austin, Texas, Forente stater, 78705
        • Aktiv, ikke rekrutterende
        • Texas Oncology - Austin
      • Dallas, Texas, Forente stater, 75390
        • Aktiv, ikke rekrutterende
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Forente stater, 77030
        • Aktiv, ikke rekrutterende
        • University of Texas - MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, Forente stater, 84112
        • Rekruttering
        • University of Utah - Huntsman Cancer Institute
        • Hovedetterforsker:
          • Howard Colman, MD, PhD
        • Ta kontakt med:
        • Ta kontakt med:
    • Virginia
      • Charlottesville, Virginia, Forente stater, 22908
        • Rekruttering
        • University of Virginia Health
        • Ta kontakt med:
        • Hovedetterforsker:
          • David Schiff, MD
    • Washington
      • Seattle, Washington, Forente stater, 98101
        • Aktiv, ikke rekrutterende
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, Forente stater, 53226
        • Rekruttering
        • Froedtert Hospital/Medical College of Wisconsin
        • Hovedetterforsker:
          • Jennifer Connelly, MD
        • Ta kontakt med:
        • Ta kontakt med:
  • Frankrike
      • Bron, Frankrike, 69677
        • Rekruttering
        • Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
        • Hovedetterforsker:
          • Francois Ducray, MD
        • Ta kontakt med:
      • Marseille, Frankrike, 13005
        • Rekruttering
        • Hopital de la Timone
        • Ta kontakt med:
        • Hovedetterforsker:
          • Emelie Tabouret, MD
      • Paris, Frankrike, 75013
        • Rekruttering
        • Hopital Piti-Salpetriere
        • Ta kontakt med:
        • Hovedetterforsker:
          • Mehdi Touat, MD
  • Sveits
      • Zurich, Sveits
        • Rekruttering
        • University Hospital Zurich
        • Hovedetterforsker:
          • Michael Weller, MD
        • Ta kontakt med:
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Sveits, 1011
        • Rekruttering
        • Centre Hospitalier Universitaire Vaudois Lausanne
        • Hovedetterforsker:
          • Andreas Hottinger, MD
        • Ta kontakt med:
  • Tyskland
      • Cologne, Tyskland, 50937
        • Rekruttering
        • Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
        • Ta kontakt med:
        • Hovedetterforsker:
          • Norbert Galldiks, Prof.
      • Frankfurt, Tyskland, 60528
        • Rekruttering
        • Dr. Senckenbergisches Institut für Neuroonkologie
        • Ta kontakt med:
        • Hovedetterforsker:
          • Michael Ronellenfitsch, MD, PhD
      • Heidelberg, Tyskland, 69120
        • Rekruttering
        • Universitätsklinik Heidelberg
        • Hovedetterforsker:
          • Antje Wick, MD
        • Ta kontakt med:
      • Mannheim, Tyskland, 68167
        • Rekruttering
        • Universitaetsklinikum Heidelberg - Neurologische Klinik
        • Hovedetterforsker:
          • Michael Platten, MD
        • Ta kontakt med:
      • Regensburg, Tyskland, 93053
        • Rekruttering
        • Universitätsklinikum Regensburg
        • Hovedetterforsker:
          • Peter Hau, MD
        • Ta kontakt med:
      • Tübingen, Tyskland, 72076
        • Rekruttering
        • Universitätsklinikum Tübingen
        • Hovedetterforsker:
          • Ghazaleh Tabatabai, MD
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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, or 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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: 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.
Legemiddel: Temozolomide

Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg

Andre navn:
  • Temodar
  • Temodal
  • Temcad
Legemiddel: Lomustine

Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg

Andre navn:
  • CCNU
  • CeeNU
  • Gleostine
Stråling: Radiation

60 Gy
Eksperimentell: 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).
Legemiddel: 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)

Andre navn:
  • BAY 73-4506
  • Stivarga
Eksperimentell: 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.
Legemiddel: 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

Andre navn:
  • GDC-0084
Eksperimentell: 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.
Legemiddel: 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.

Andre navn:
  • Dianhydrogalaktitol
Eksperimentell: 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.
Legemiddel: 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.
Eksperimentell: 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.
Legemiddel: 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.
Eksperimentell: 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.
Legemiddel: 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.
Eksperimentell: 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.
Legemiddel: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andre navn:
  • BHV-4157
Eksperimentell: 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.
Legemiddel: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andre navn:
  • BHV-4157
Eksperimentell: 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.
Legemiddel: Troriluzole

Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

Andre navn:
  • BHV-4157
Eksperimentell: 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.
Biologisk: 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

Andre navn:
  • Pegargiminase
Eksperimentell: 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.
Biologisk: 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

Andre navn:
  • Pegargiminase
Eksperimentell: 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.
Biologisk: 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

Andre navn:
  • Pegargiminase
Eksperimentell: 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.
Legemiddel: AZD1390

Standard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.
Eksperimentell: 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).
Legemiddel: 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.

Andre navn:
  • EDO-S101
Eksperimentell: 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.
Legemiddel: 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.

Andre navn:
  • EDO-S101
Eksperimentell: 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.
Legemiddel: 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.

Andre navn:
  • EDO-S101

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Overall Survival (OS)
Tidsramme: 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.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-free survival (PFS)
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Global Coalition for Adaptive Research

Samarbeidspartnere

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

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

30. juli 2019

Primær fullføring (Antatt)

1. juni 2028

Studiet fullført (Antatt)

1. juni 2030

Datoer for studieregistrering

Først innsendt

23. mai 2019

Først innsendt som oppfylte QC-kriteriene

30. mai 2019

Først lagt ut (Faktiske)

31. mai 2019

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

2. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

29. oktober 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • GCAR-7213

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

UBESLUTTE

IPD-planbeskrivelse

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

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere