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在新诊断和复发性胶质母细胞瘤中评估多种方案的试验 (GBM AGILE)

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

GBM AGILE：全球适应性试验主方案：国际无缝 II/III 期响应适应性随机化平台试验，旨在评估新诊断和复发性 GBM 的多种治疗方案

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 (*).

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

2250

阶段

  • 阶段2
  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

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

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
有源比较器：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.
药品：Temozolomide

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

其他名称：
  • 特莫达尔
  • 泰莫达
  • Temcad软件
药品：Lomustine

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

其他名称：
  • 中央师范大学
  • 中大
  • 皂甙
辐射：Radiation

60 Gy
实验性的：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).
药品：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)

其他名称：
  • 海湾 73-4506
  • 斯蒂瓦尔加
实验性的：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.
药品：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

其他名称：
  • GDC-0084
实验性的：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.
药品：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.

其他名称：
  • 二氢半乳糖醇
实验性的：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.
药品：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.
实验性的：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.
药品：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.
实验性的：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.
药品：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.
实验性的：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.
药品：Troriluzole

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

其他名称：
  • BHV-4157
实验性的：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.
药品：Troriluzole

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

其他名称：
  • BHV-4157
实验性的：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.
药品：Troriluzole

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

其他名称：
  • BHV-4157
实验性的：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：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

其他名称：
  • 聚乙二醇胺酶
实验性的：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：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

其他名称：
  • 聚乙二醇胺酶
实验性的：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：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

其他名称：
  • 聚乙二醇胺酶
实验性的：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.
药品：AZD1390

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

其他名称：
  • EDO-S101
实验性的：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.
药品：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.

其他名称：
  • EDO-S101
实验性的：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.
药品：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.

其他名称：
  • EDO-S101

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Overall Survival (OS)
大体时间：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.

次要结果测量

结果测量
措施说明
大体时间
Progression-free survival (PFS)
大体时间：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
大体时间：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)
大体时间：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.

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Global Coalition for Adaptive Research

合作者

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

调查人员

  • 首席研究员：Tim Cloughesy, MD、GCAR CMO and GBM AGILE Global PI

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2019年7月30日

初级完成 (估计的)

2028年6月1日

研究完成 (估计的)

2030年6月1日

研究注册日期

首次提交

2019年5月23日

首先提交符合 QC 标准的

2019年5月30日

首次发布 (实际的)

2019年5月31日

研究记录更新

最后更新发布 (实际的)

2026年11月2日

上次提交的符合 QC 标准的更新

2026年10月29日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • GCAR-7213

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

IPD 计划说明

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

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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