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Un ensayo para evaluar múltiples regímenes en glioblastoma recién diagnosticado y recurrente (GBM AGILE)

29 de octubre de 2026 actualizado por: Global Coalition for Adaptive Research

GBM AGILE: Global Adaptive Trial Master Protocol: un ensayo internacional de plataforma de aleatorización adaptativa de respuesta de fase II/III sin fisuras diseñado para evaluar múltiples regímenes en GBM recién diagnosticado y recurrente

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 (*).

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

2250

Fase

  • Fase 2
  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Copia de seguridad de contactos de estudio

Ubicaciones de estudio

  • Alemania
      • Cologne, Alemania, 50937
        • Reclutamiento
        • Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
        • Contacto:
        • Investigador principal:
          • Norbert Galldiks, Prof.
      • Frankfurt, Alemania, 60528
        • Reclutamiento
        • Dr. Senckenbergisches Institut für Neuroonkologie
        • Contacto:
        • Investigador principal:
          • Michael Ronellenfitsch, MD, PhD
      • Heidelberg, Alemania, 69120
        • Reclutamiento
        • Universitätsklinik Heidelberg
        • Investigador principal:
          • Antje Wick, MD
        • Contacto:
      • Mannheim, Alemania, 68167
        • Reclutamiento
        • Universitaetsklinikum Heidelberg - Neurologische Klinik
        • Investigador principal:
          • Michael Platten, MD
        • Contacto:
          • Yvonne Neu
          • Número de teléfono: +49 621 383-6801
          • Correo electrónico: yvonne.neu@umm.de
      • Regensburg, Alemania, 93053
        • Reclutamiento
        • Universitätsklinikum Regensburg
        • Investigador principal:
          • Peter Hau, MD
        • Contacto:
          • Peter Hau, MD
          • Número de teléfono: +49 (0)941 941-8083
          • Correo electrónico: Peter.Hau@ukr.de
      • Tübingen, Alemania, 72076
        • Reclutamiento
        • Universitätsklinikum Tübingen
        • Investigador principal:
          • Ghazaleh Tabatabai, MD
        • Contacto:
  • Australia
    • New South Wales
      • St Leonards, New South Wales, Australia, 2065
        • Reclutamiento
        • Northern Sydney Cancer Centre/Royal North Shore Hospital
        • Investigador principal:
          • Helen Wheeler, MD
        • Contacto:
      • Waratah, New South Wales, Australia, 2298
        • Activo, no reclutando
        • Calvary Mater Newcastle
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Reclutamiento
        • Royal Brisbane and Women's Hospital
        • Investigador principal:
          • Zarnie Lwin, MD
        • Contacto:
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Reclutamiento
        • Flinders Medical Centre
        • Investigador principal:
          • Ganessan Kichenadasse, MD
        • Contacto:
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Reclutamiento
        • Austin Health
        • Investigador principal:
          • Hui Gan, MBBS, FRACP, PhD
        • Contacto:
        • Contacto:
      • Melbourne, Victoria, Australia
        • Reclutamiento
        • Peter MacCallum Cancer Centre
        • Investigador principal:
          • Jim Whittle, MD
        • Contacto:
        • Contacto:
  • Canadá
    • Ontario
      • Toronto, Ontario, Canadá, M4N 3M5
        • Reclutamiento
        • Sunnybrook Health Sciences Centre
        • Contacto:
        • Investigador principal:
          • James Perry, MD, FRCPC
        • Contacto:
      • Toronto, Ontario, Canadá, M5G 2C1
        • Reclutamiento
        • Princess Margaret Cancer Centre
        • Investigador principal:
          • Warren Mason, MD
        • Contacto:
          • On Yee Jones, RN
          • Número de teléfono: 4603 416-946-4501
          • Correo electrónico: onyee.jones@uhn.ca
        • Contacto:
    • Quebec
      • Montreal, Quebec, Canadá, H3A 2B4
        • Activo, no reclutando
        • Montreal Neurological Institute and Hospital, McGill University
      • Sherbrooke, Quebec, Canadá, J1H 5H3
        • Activo, no reclutando
        • Université de Sherbrooke
  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos, 35249
        • Reclutamiento
        • University of Alabama at Birmingham
        • Investigador principal:
          • Louis B Nabors, MD
        • Contacto:
          • Thiru Pillay
          • Número de teléfono: 205-934-1432
          • Correo electrónico: Tpillay@uabmc.edu
        • Contacto:
    • California
      • La Jolla, California, Estados Unidos, 92093
        • Reclutamiento
        • University of California, San Diego
        • Investigador principal:
          • David Piccioni, MD, PhD
        • Contacto:
        • Contacto:
      • Los Angeles, California, Estados Unidos, 90048
        • Activo, no reclutando
        • Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
      • Los Angeles, California, Estados Unidos, 90095
        • Activo, no reclutando
        • University of California, Los Angeles
      • Orange, California, Estados Unidos, 92868
        • Reclutamiento
        • St. Joseph Hospital
        • Investigador principal:
          • Lars Anker, MD
        • Contacto:
      • San Francisco, California, Estados Unidos, 94143
        • Reclutamiento
        • University of California, San Francisco
        • Investigador principal:
          • Nicholas Butowski, MD
        • Contacto:
      • Stanford, California, Estados Unidos, 94305
        • Terminado
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80045
        • Reclutamiento
        • University of Colorado Denver
        • Investigador principal:
          • Denise Damek, MD
        • Contacto:
    • Connecticut
      • New Haven, Connecticut, Estados Unidos, 06511
        • Reclutamiento
        • Yale Cancer Center / Smilow Cancer Hospital*
        • Investigador principal:
          • Nicholas Blondin, MD
        • Contacto:
    • Florida
      • Jacksonville, Florida, Estados Unidos, 32224
        • Terminado
        • Mayo Clinic Cancer Center
      • Miami, Florida, Estados Unidos, 33136
        • Reclutamiento
        • Sylvester Comprehensive Cancer Center*
        • Investigador principal:
          • Macarena I De La Fuente, MD
        • Contacto:
      • Tampa, Florida, Estados Unidos, 33612
        • Reclutamiento
        • Moffitt Cancer Center
        • Investigador principal:
          • Patrick Grogan, MD
        • Contacto:
        • Contacto:
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30309
        • Activo, no reclutando
        • Piedmont Atlanta Hospital
      • Atlanta, Georgia, Estados Unidos, 30322
        • Activo, no reclutando
        • Winship Cancer Institute of Emory University
    • Louisiana
      • New Orleans, Louisiana, Estados Unidos, 70112
        • Terminado
        • LSU Health Sciences Center - New Orleans
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02114
        • Reclutamiento
        • Massachusetts General Hospital
        • Investigador principal:
          • Patrick Wen, MD
        • Contacto:
          • Patrick Wen, MD
          • Número de teléfono: 617-726-5130
          • Correo electrónico: pwen@mgb.org
      • Boston, Massachusetts, Estados Unidos, 02115
    • Michigan
      • Detroit, Michigan, Estados Unidos, 48202
        • Terminado
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos, 55407
        • Reclutamiento
        • Allina Health Systems/Abbott Northwestern Hospital
        • Investigador principal:
          • Andrea Wasilewski, MD
        • Contacto:
      • Rochester, Minnesota, Estados Unidos, 55905
        • Terminado
        • Mayo Clinic Cancer Center - Rochester
    • Mississippi
      • Jackson, Mississippi, Estados Unidos, 39213
        • Terminado
        • University of Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, Estados Unidos, 63110
        • Terminado
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • New York, New York, Estados Unidos, 10032
        • Reclutamiento
        • Columbia University Medical Center
        • Investigador principal:
          • Andrew Lassman, MD
        • Contacto:
      • New York, New York, Estados Unidos, 10016
        • Activo, no reclutando
        • Perlmutter Cancer Center, NYU Langone Health
      • New York, New York, Estados Unidos, 10029
        • Activo, no reclutando
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, Estados Unidos, 10065
        • Reclutamiento
        • Memorial Sloan Kettering Cancer Center*
        • Investigador principal:
          • Ingo Mellinghoff, MD
        • Contacto:
          • Kerina Yang
          • Número de teléfono: 901-883-0840
          • Correo electrónico: yangk3@mskcc.org
        • Contacto:
          • Nancy Keith
          • Número de teléfono: 646-300-0216
          • Correo electrónico: KeithN@mskcc.org
    • North Carolina
      • Durham, North Carolina, Estados Unidos, 27710
        • Activo, no reclutando
        • Duke University Medical Center
      • Winston-Salem, North Carolina, Estados Unidos, 272157
        • Reclutamiento
        • Comprehensive Cancer Center of Wake Forest*
        • Investigador principal:
          • Glenn Lesser, MD
        • Contacto:
    • Ohio
      • Cleveland, Ohio, Estados Unidos, 44195
        • Reclutamiento
        • Cleveland Clinic
        • Investigador principal:
          • Mina Lobbous, MD
        • Contacto:
          • Kathy Robinson
          • Número de teléfono: 216-444-8923
          • Correo electrónico: robinsk2@ccf.org
        • Contacto:
          • Rachel Hufsey
          • Número de teléfono: 216-442-6671
          • Correo electrónico: HUFSEYR@ccf.org
      • Cleveland, Ohio, Estados Unidos, 44106
        • Reclutamiento
        • University Hospitals Cleveland Medical Center*
        • Investigador principal:
          • Herbert Newton, MD
        • Contacto:
        • Contacto:
      • Columbus, Ohio, Estados Unidos, 43210
        • Activo, no reclutando
        • Ohio State University Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
        • Activo, no reclutando
        • University of Pennsylvania - Perelman Center for Advanced Medicine
      • Pittsburgh, Pennsylvania, Estados Unidos, 15232
        • Activo, no reclutando
        • University of Pittsburgh Medical Center - Hillman Cancer Center
      • Pittsburgh, Pennsylvania, Estados Unidos, 15212
        • Terminado
        • Allegheny General Hospital
    • South Carolina
      • Charleston, South Carolina, Estados Unidos, 29425
        • Reclutamiento
        • Medical University of South Carolina - Hollings Cancer Center
        • Investigador principal:
          • Scott Lindhorst, MD
        • Contacto:
    • Texas
      • Austin, Texas, Estados Unidos, 78705
        • Activo, no reclutando
        • Texas Oncology - Austin
      • Dallas, Texas, Estados Unidos, 75390
        • Activo, no reclutando
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Estados Unidos, 77030
        • Activo, no reclutando
        • University of Texas - MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, Estados Unidos, 84112
        • Reclutamiento
        • University of Utah - Huntsman Cancer Institute
        • Investigador principal:
          • Howard Colman, MD, PhD
        • Contacto:
        • Contacto:
    • Virginia
      • Charlottesville, Virginia, Estados Unidos, 22908
        • Reclutamiento
        • University of Virginia Health
        • Contacto:
        • Investigador principal:
          • David Schiff, MD
    • Washington
      • Seattle, Washington, Estados Unidos, 98101
        • Activo, no reclutando
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, Estados Unidos, 53226
        • Reclutamiento
        • Froedtert Hospital/Medical College of Wisconsin
        • Investigador principal:
          • Jennifer Connelly, MD
        • Contacto:
          • Chris Fueger
          • Número de teléfono: 414-805-8837
          • Correo electrónico: cfueger@mcw.edu
        • Contacto:
          • Bailee Fritz
          • Número de teléfono: 414-805-8939
          • Correo electrónico: bfritz@mcw.edu
  • Francia
      • Bron, Francia, 69677
        • Reclutamiento
        • Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
        • Investigador principal:
          • Francois Ducray, MD
        • Contacto:
      • Marseille, Francia, 13005
        • Reclutamiento
        • Hopital de la Timone
        • Contacto:
        • Investigador principal:
          • Emelie Tabouret, MD
      • Paris, Francia, 75013
        • Reclutamiento
        • Hopital Piti-Salpetriere
        • Contacto:
          • Mehdi Touat, MD
          • Número de teléfono: +33 (0)1 42 16 03 81
          • Correo electrónico: mehdi.touat@ahph.fr
        • Investigador principal:
          • Mehdi Touat, MD
  • Suiza
      • Zurich, Suiza
        • Reclutamiento
        • University Hospital Zurich
        • Investigador principal:
          • Michael Weller, MD
        • Contacto:
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Suiza, 1011
        • Reclutamiento
        • Centre Hospitalier Universitaire Vaudois Lausanne
        • Investigador principal:
          • Andreas Hottinger, MD
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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 de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación Secuencial
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: 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.
Droga: Temozolomide

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

Otros nombres:
  • Temodar
  • Temodal
  • Temcad
Droga: Lomustine

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

Otros nombres:
  • CCNU
  • CeeNU
  • Gleostina
Radiación: Radiation

60 Gy
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).
Droga: 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)

Otros nombres:
  • BAHÍA 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.
Droga: 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

Otros nombres:
  • 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.
Droga: 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.

Otros nombres:
  • Dianhidrogalactitol
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.
Droga: 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.
Droga: 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

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.
Droga: 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.
Droga: Troriluzole

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

Otros nombres:
  • 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.
Droga: Troriluzole

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

Otros nombres:
  • BHV-4157
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.
Droga: Troriluzole

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

Otros nombres:
  • BHV-4157
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.
Biológico: 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

Otros nombres:
  • Pegargiminasa
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.
Biológico: 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

Otros nombres:
  • Pegargiminasa
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.
Biológico: 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

Otros nombres:
  • Pegargiminasa
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.
Droga: AZD1390

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

Otros nombres:
  • 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.
Droga: 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.

Otros nombres:
  • 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.
Droga: 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.

Otros nombres:
  • EDO-S101

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Overall Survival (OS)
Periodo de tiempo: 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.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Progression-free survival (PFS)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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.

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Global Coalition for Adaptive Research

Colaboradores

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

Investigadores

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

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Enlaces Útiles

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

30 de julio de 2019

Finalización primaria (Estimado)

1 de junio de 2028

Finalización del estudio (Estimado)

1 de junio de 2030

Fechas de registro del estudio

Enviado por primera vez

23 de mayo de 2019

Primero enviado que cumplió con los criterios de control de calidad

30 de mayo de 2019

Publicado por primera vez (Actual)

31 de mayo de 2019

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

2 de noviembre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

29 de octubre de 2026

Última verificación

1 de junio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • GCAR-7213

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

INDECISO

Descripción del plan IPD

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

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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