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Ett försök för att utvärdera flera regimer vid nyligen diagnostiserat och återkommande glioblastom (GBM AGILE)

29 oktober 2026 uppdaterad av: Global Coalition for Adaptive Research

GBM AGILE: Global Adaptive Trial Master Protocol: En internationell, sömlös fas II/III Response Adaptive Randomization Platform Trial utformad för att utvärdera flera regimer i nydiagnostiserade och återkommande 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 (*).

Studieöversikt

Status

Rekrytering

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Beräknad)

2250

Fas

  • Fas 2
  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Sekventiell tilldelning
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / 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.
Läkemedel: Temozolomide

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

Andra namn:
  • Temodar
  • Temodal
  • Temcad
Läkemedel: Lomustine

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

Andra namn:
  • CCNU
  • CeeNU
  • Gleostin
Strålning: Radiation

60 Gy
Experimentell: 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).
Läkemedel: 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)

Andra namn:
  • BAY 73-4506
  • Stivarga
Experimentell: 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.
Läkemedel: 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

Andra namn:
  • GDC-0084
Experimentell: 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.
Läkemedel: 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.

Andra namn:
  • Dianhydrogalaktitol
Experimentell: 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.
Läkemedel: 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.
Experimentell: 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.
Läkemedel: 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.
Experimentell: 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.
Läkemedel: 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.
Experimentell: 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.
Läkemedel: Troriluzole

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

Andra namn:
  • BHV-4157
Experimentell: 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.
Läkemedel: Troriluzole

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

Andra namn:
  • BHV-4157
Experimentell: 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.
Läkemedel: Troriluzole

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

Andra namn:
  • BHV-4157
Experimentell: 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

Andra namn:
  • Pegargiminas
Experimentell: 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

Andra namn:
  • Pegargiminas
Experimentell: 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

Andra namn:
  • Pegargiminas
Experimentell: 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.
Läkemedel: AZD1390

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

Andra namn:
  • EDO-S101
Experimentell: 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.
Läkemedel: 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.

Andra namn:
  • EDO-S101
Experimentell: 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.
Läkemedel: 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.

Andra namn:
  • EDO-S101

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Overall Survival (OS)
Tidsram: 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.

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Progression-free survival (PFS)
Tidsram: 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
Tidsram: 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)
Tidsram: 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.

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Global Coalition for Adaptive Research

Samarbetspartners

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

Utredare

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

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

30 juli 2019

Primärt slutförande (Beräknad)

1 juni 2028

Avslutad studie (Beräknad)

1 juni 2030

Studieregistreringsdatum

Först inskickad

23 maj 2019

Först inskickad som uppfyllde QC-kriterierna

30 maj 2019

Första postat (Faktisk)

31 maj 2019

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

2 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

29 oktober 2026

Senast verifierad

1 juni 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • GCAR-7213

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

OBESLUTSAM

IPD-planbeskrivning

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

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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