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Un essai pour évaluer plusieurs régimes dans le glioblastome nouvellement diagnostiqué et récurrent (GBM AGILE)

29 octobre 2026 mis à jour par: Global Coalition for Adaptive Research

GBM AGILE : Global Adaptive Trial Master Protocol : un essai international de plate-forme de randomisation adaptative de réponse de phase II/III homogène conçu pour évaluer plusieurs régimes dans le GBM nouvellement diagnostiqué et récurrent

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 (*).

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

2250

Phase

  • Phase 2
  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • Allemagne
      • Cologne, Allemagne, 50937
        • Recrutement
        • Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
        • Contact:
        • Chercheur principal:
          • Norbert Galldiks, Prof.
      • Frankfurt, Allemagne, 60528
        • Recrutement
        • Dr. Senckenbergisches Institut für Neuroonkologie
        • Contact:
        • Chercheur principal:
          • Michael Ronellenfitsch, MD, PhD
      • Heidelberg, Allemagne, 69120
        • Recrutement
        • Universitätsklinik Heidelberg
        • Chercheur principal:
          • Antje Wick, MD
        • Contact:
      • Mannheim, Allemagne, 68167
        • Recrutement
        • Universitaetsklinikum Heidelberg - Neurologische Klinik
        • Chercheur principal:
          • Michael Platten, MD
        • Contact:
      • Regensburg, Allemagne, 93053
        • Recrutement
        • Universitätsklinikum Regensburg
        • Chercheur principal:
          • Peter Hau, MD
        • Contact:
          • Peter Hau, MD
          • Numéro de téléphone: +49 (0)941 941-8083
          • E-mail: Peter.Hau@ukr.de
      • Tübingen, Allemagne, 72076
        • Recrutement
        • Universitätsklinikum Tübingen
        • Chercheur principal:
          • Ghazaleh Tabatabai, MD
        • Contact:
  • Australie
    • New South Wales
      • St Leonards, New South Wales, Australie, 2065
        • Recrutement
        • Northern Sydney Cancer Centre/Royal North Shore Hospital
        • Chercheur principal:
          • Helen Wheeler, MD
        • Contact:
      • Waratah, New South Wales, Australie, 2298
        • Actif, ne recrute pas
        • Calvary Mater Newcastle
    • Queensland
      • Herston, Queensland, Australie, 4029
        • Recrutement
        • Royal Brisbane and Women's Hospital
        • Chercheur principal:
          • Zarnie Lwin, MD
        • Contact:
    • South Australia
      • Bedford Park, South Australia, Australie, 5042
    • Victoria
      • Heidelberg, Victoria, Australie, 3084
      • Melbourne, Victoria, Australie
        • Recrutement
        • Peter MacCallum Cancer Centre
        • Chercheur principal:
          • Jim Whittle, MD
        • Contact:
        • Contact:
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
      • Toronto, Ontario, Canada, M5G 2C1
        • Recrutement
        • Princess Margaret Cancer Centre
        • Chercheur principal:
          • Warren Mason, MD
        • Contact:
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Actif, ne recrute pas
        • Montreal Neurological Institute and Hospital, McGill University
      • Sherbrooke, Quebec, Canada, J1H 5H3
        • Actif, ne recrute pas
        • Université de Sherbrooke
  • France
      • Bron, France, 69677
        • Recrutement
        • Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
        • Chercheur principal:
          • Francois Ducray, MD
        • Contact:
      • Marseille, France, 13005
        • Recrutement
        • Hopital de la Timone
        • Contact:
        • Chercheur principal:
          • Emelie Tabouret, MD
      • Paris, France, 75013
        • Recrutement
        • Hopital Piti-Salpetriere
        • Contact:
        • Chercheur principal:
          • Mehdi Touat, MD
  • Suisse
      • Zurich, Suisse
        • Recrutement
        • University Hospital Zurich
        • Chercheur principal:
          • Michael Weller, MD
        • Contact:
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Suisse, 1011
        • Recrutement
        • Centre Hospitalier Universitaire Vaudois Lausanne
        • Chercheur principal:
          • Andreas Hottinger, MD
        • Contact:
  • États-Unis
    • Alabama
      • Birmingham, Alabama, États-Unis, 35249
        • Recrutement
        • University of Alabama at Birmingham
        • Chercheur principal:
          • Louis B Nabors, MD
        • Contact:
        • Contact:
    • California
      • La Jolla, California, États-Unis, 92093
      • Los Angeles, California, États-Unis, 90048
        • Actif, ne recrute pas
        • Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
      • Los Angeles, California, États-Unis, 90095
        • Actif, ne recrute pas
        • University of California, Los Angeles
      • Orange, California, États-Unis, 92868
        • Recrutement
        • St. Joseph Hospital
        • Chercheur principal:
          • Lars Anker, MD
        • Contact:
      • San Francisco, California, États-Unis, 94143
        • Recrutement
        • University of California, San Francisco
        • Chercheur principal:
          • Nicholas Butowski, MD
        • Contact:
      • Stanford, California, États-Unis, 94305
        • Complété
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, États-Unis, 80045
        • Recrutement
        • University of Colorado Denver
        • Chercheur principal:
          • Denise Damek, MD
        • Contact:
    • Connecticut
      • New Haven, Connecticut, États-Unis, 06511
        • Recrutement
        • Yale Cancer Center / Smilow Cancer Hospital*
        • Chercheur principal:
          • Nicholas Blondin, MD
        • Contact:
    • Florida
      • Jacksonville, Florida, États-Unis, 32224
        • Complété
        • Mayo Clinic Cancer Center
      • Miami, Florida, États-Unis, 33136
        • Recrutement
        • Sylvester Comprehensive Cancer Center*
        • Chercheur principal:
          • Macarena I De La Fuente, MD
        • Contact:
      • Tampa, Florida, États-Unis, 33612
        • Recrutement
        • Moffitt Cancer Center
        • Chercheur principal:
          • Patrick Grogan, MD
        • Contact:
        • Contact:
    • Georgia
      • Atlanta, Georgia, États-Unis, 30309
        • Actif, ne recrute pas
        • Piedmont Atlanta Hospital
      • Atlanta, Georgia, États-Unis, 30322
        • Actif, ne recrute pas
        • Winship Cancer Institute of Emory University
    • Louisiana
      • New Orleans, Louisiana, États-Unis, 70112
        • Complété
        • LSU Health Sciences Center - New Orleans
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02114
        • Recrutement
        • Massachusetts General Hospital
        • Chercheur principal:
          • Patrick Wen, MD
        • Contact:
          • Patrick Wen, MD
          • Numéro de téléphone: 617-726-5130
          • E-mail: pwen@mgb.org
      • Boston, Massachusetts, États-Unis, 02115
    • Michigan
      • Detroit, Michigan, États-Unis, 48202
        • Complété
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, États-Unis, 55407
        • Recrutement
        • Allina Health Systems/Abbott Northwestern Hospital
        • Chercheur principal:
          • Andrea Wasilewski, MD
        • Contact:
      • Rochester, Minnesota, États-Unis, 55905
        • Complété
        • Mayo Clinic Cancer Center - Rochester
    • Mississippi
      • Jackson, Mississippi, États-Unis, 39213
        • Complété
        • University of Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, États-Unis, 63110
        • Complété
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • New York, New York, États-Unis, 10032
        • Recrutement
        • Columbia University Medical Center
        • Chercheur principal:
          • Andrew Lassman, MD
        • Contact:
      • New York, New York, États-Unis, 10016
        • Actif, ne recrute pas
        • Perlmutter Cancer Center, NYU Langone Health
      • New York, New York, États-Unis, 10029
        • Actif, ne recrute pas
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, États-Unis, 10065
        • Recrutement
        • Memorial Sloan Kettering Cancer Center*
        • Chercheur principal:
          • Ingo Mellinghoff, MD
        • Contact:
        • Contact:
    • North Carolina
      • Durham, North Carolina, États-Unis, 27710
        • Actif, ne recrute pas
        • Duke University Medical Center
      • Winston-Salem, North Carolina, États-Unis, 272157
        • Recrutement
        • Comprehensive Cancer Center of Wake Forest*
        • Chercheur principal:
          • Glenn Lesser, MD
        • Contact:
    • Ohio
      • Cleveland, Ohio, États-Unis, 44195
        • Recrutement
        • Cleveland Clinic
        • Chercheur principal:
          • Mina Lobbous, MD
        • Contact:
        • Contact:
          • Rachel Hufsey
          • Numéro de téléphone: 216-442-6671
          • E-mail: HUFSEYR@ccf.org
      • Cleveland, Ohio, États-Unis, 44106
      • Columbus, Ohio, États-Unis, 43210
        • Actif, ne recrute pas
        • Ohio State University Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, États-Unis, 19104
        • Actif, ne recrute pas
        • University of Pennsylvania - Perelman Center for Advanced Medicine
      • Pittsburgh, Pennsylvania, États-Unis, 15232
        • Actif, ne recrute pas
        • University of Pittsburgh Medical Center - Hillman Cancer Center
      • Pittsburgh, Pennsylvania, États-Unis, 15212
        • Complété
        • Allegheny General Hospital
    • South Carolina
      • Charleston, South Carolina, États-Unis, 29425
        • Recrutement
        • Medical University of South Carolina - Hollings Cancer Center
        • Chercheur principal:
          • Scott Lindhorst, MD
        • Contact:
    • Texas
      • Austin, Texas, États-Unis, 78705
        • Actif, ne recrute pas
        • Texas Oncology - Austin
      • Dallas, Texas, États-Unis, 75390
        • Actif, ne recrute pas
        • University of Texas Southwestern Medical Center
      • Houston, Texas, États-Unis, 77030
        • Actif, ne recrute pas
        • University of Texas - MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, États-Unis, 84112
        • Recrutement
        • University of Utah - Huntsman Cancer Institute
        • Chercheur principal:
          • Howard Colman, MD, PhD
        • Contact:
        • Contact:
    • Virginia
      • Charlottesville, Virginia, États-Unis, 22908
        • Recrutement
        • University of Virginia Health
        • Contact:
        • Chercheur principal:
          • David Schiff, MD
    • Washington
      • Seattle, Washington, États-Unis, 98101
        • Actif, ne recrute pas
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, États-Unis, 53226
        • Recrutement
        • Froedtert Hospital/Medical College of Wisconsin
        • Chercheur principal:
          • Jennifer Connelly, MD
        • Contact:
          • Chris Fueger
          • Numéro de téléphone: 414-805-8837
          • E-mail: cfueger@mcw.edu
        • Contact:
          • Bailee Fritz
          • Numéro de téléphone: 414-805-8939
          • E-mail: bfritz@mcw.edu

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La 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, 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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: 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.
Médicament: Temozolomide

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

Autres noms:
  • Témodar
  • Temodal
  • Temcad
Médicament: Lomustine

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

Autres noms:
  • CCNU
  • CeeNU
  • Gléostine
Radiation: Radiation

60 Gy
Expérimental: 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).
Médicament: 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)

Autres noms:
  • BAIE 73-4506
  • Stivarga
Expérimental: 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.
Médicament: 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

Autres noms:
  • GDC-0084
Expérimental: 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.
Médicament: 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.

Autres noms:
  • Dianhydrogalactitol
Expérimental: 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.
Médicament: 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.
Expérimental: 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.
Médicament: 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.
Expérimental: 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.
Médicament: 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.
Expérimental: 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.
Médicament: Troriluzole

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

Autres noms:
  • BHV-4157
Expérimental: 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.
Médicament: Troriluzole

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

Autres noms:
  • BHV-4157
Expérimental: 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.
Médicament: Troriluzole

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

Autres noms:
  • BHV-4157
Expérimental: 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.
Biologique: 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

Autres noms:
  • Pégargiminase
Expérimental: 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.
Biologique: 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

Autres noms:
  • Pégargiminase
Expérimental: 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.
Biologique: 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

Autres noms:
  • Pégargiminase
Expérimental: 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.
Médicament: AZD1390

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

Autres noms:
  • EDO-S101
Expérimental: 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.
Médicament: 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.

Autres noms:
  • EDO-S101
Expérimental: 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.
Médicament: 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.

Autres noms:
  • EDO-S101

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Overall Survival (OS)
Délai: 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.

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Progression-free survival (PFS)
Délai: 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
Délai: 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)
Délai: 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.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Global Coalition for Adaptive Research

Collaborateurs

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

Les enquêteurs

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

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

30 juillet 2019

Achèvement primaire (Estimé)

1 juin 2028

Achèvement de l'étude (Estimé)

1 juin 2030

Dates d'inscription aux études

Première soumission

23 mai 2019

Première soumission répondant aux critères de contrôle qualité

30 mai 2019

Première publication (Réel)

31 mai 2019

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

2 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

29 octobre 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • GCAR-7213

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

INDÉCIS

Description du régime IPD

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

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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