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新たに診断され再発した膠芽腫における複数のレジメンを評価する試験 (GBM AGILE)

2026年10月29日 更新者：Global Coalition for Adaptive Research

GBM AGILE: グローバル アダプティブ トライアル マスター プロトコル: 新たに診断された再発性 GBM における複数のレジメンを評価するために設計された、国際的なシームレスな第 II/III 相対応アダプティブ ランダム化プラットフォーム試験

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 (*).

調査の概要

状態

募集

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (推定)

2250

段階

  • フェーズ2
  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

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

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：順次割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
アクティブコンパレータ：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.
薬：Temozolomide

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

他の名前：
  • テモダール
  • テモーダル
  • Temcad
薬：Lomustine

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

他の名前：
  • CCNU
  • シーヌ
  • グレオスティン
放射線：Radiation

60 Gy
実験的：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).
薬：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)

他の名前：
  • ベイ 73-4506
  • スティヴァルガ
実験的：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.
薬：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

他の名前：
  • GDC-0084
実験的：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.
薬：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.

他の名前：
  • ジアンヒドロガラクチトール
実験的：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.
薬：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.
実験的：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.
薬：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.
実験的：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.
薬：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.
実験的：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.
薬：Troriluzole

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

他の名前：
  • BHV-4157
実験的：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.
薬：Troriluzole

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

他の名前：
  • BHV-4157
実験的：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.
薬：Troriluzole

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

他の名前：
  • BHV-4157
実験的：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.
生物学的：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

他の名前：
  • ペガルギミナーゼ
実験的：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.
生物学的：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

他の名前：
  • ペガルギミナーゼ
実験的：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.
生物学的：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

他の名前：
  • ペガルギミナーゼ
実験的：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.
薬：AZD1390

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

他の名前：
  • EDO-S101
実験的：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.
薬：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.

他の名前：
  • EDO-S101
実験的：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.
薬：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.

他の名前：
  • EDO-S101

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Overall Survival (OS)
時間枠：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.

二次結果の測定

結果測定
メジャーの説明
時間枠
Progression-free survival (PFS)
時間枠：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
時間枠：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)
時間枠：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.

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Global Coalition for Adaptive Research

協力者

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

捜査官

  • 主任研究者：Tim Cloughesy, MD、GCAR CMO and GBM AGILE Global PI

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

便利なリンク

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2019年7月30日

一次修了 (推定)

2028年6月1日

研究の完了 (推定)

2030年6月1日

試験登録日

最初に提出

2019年5月23日

QC基準を満たした最初の提出物

2019年5月30日

最初の投稿 (実際)

2019年5月31日

学習記録の更新

投稿された最後の更新 (実際)

2026年11月2日

QC基準を満たした最後の更新が送信されました

2026年10月29日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • GCAR-7213

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

未定

IPD プランの説明

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

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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