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Испытание для оценки нескольких режимов при недавно диагностированной и рецидивирующей глиобластоме (GBM AGILE)

29 октября 2026 г. обновлено: Global Coalition for Adaptive Research

GBM AGILE: Global Adaptive Trial Master Protocol: международное испытание платформы адаптивной рандомизации с плавным ответом фазы II/III, предназначенное для оценки нескольких режимов при недавно диагностированной и рецидивирующей ГБМ

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 (*).

Обзор исследования

Статус

Рекрутинг

Условия

Вмешательство/лечение

Подробное описание

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.

Тип исследования

Интервенционный

Регистрация (Оцененный)

2250

Фаза

  • Фаза 2
  • Фаза 3

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

Учебное резервное копирование контактов

Места учебы

  • Австралия
    • New South Wales
      • St Leonards, New South Wales, Австралия, 2065
        • Рекрутинг
        • Northern Sydney Cancer Centre/Royal North Shore Hospital
        • Главный следователь:
          • Helen Wheeler, MD
        • Контакт:
      • Waratah, New South Wales, Австралия, 2298
        • Активный, не рекрутирующий
        • Calvary Mater Newcastle
    • Queensland
      • Herston, Queensland, Австралия, 4029
        • Рекрутинг
        • Royal Brisbane and Women's Hospital
        • Главный следователь:
          • Zarnie Lwin, MD
        • Контакт:
    • South Australia
      • Bedford Park, South Australia, Австралия, 5042
        • Рекрутинг
        • Flinders Medical Centre
        • Главный следователь:
          • Ganessan Kichenadasse, MD
        • Контакт:
    • Victoria
      • Heidelberg, Victoria, Австралия, 3084
        • Рекрутинг
        • Austin Health
        • Главный следователь:
          • Hui Gan, MBBS, FRACP, PhD
        • Контакт:
        • Контакт:
      • Melbourne, Victoria, Австралия
        • Рекрутинг
        • Peter MacCallum Cancer Centre
        • Главный следователь:
          • Jim Whittle, MD
        • Контакт:
          • Lucy Willis
          • Номер телефона: 1110289 +61 3 8559 5000
          • Электронная почта: Lucy.Willis@petermac.org
        • Контакт:
          • Iris Huang
          • Номер телефона: 1110502 +61 3 8559 5000
          • Электронная почта: Iris.Huang@petermac.org
  • Германия
      • Cologne, Германия, 50937
        • Рекрутинг
        • Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
        • Контакт:
        • Главный следователь:
          • Norbert Galldiks, Prof.
      • Frankfurt, Германия, 60528
        • Рекрутинг
        • Dr. Senckenbergisches Institut für Neuroonkologie
        • Контакт:
        • Главный следователь:
          • Michael Ronellenfitsch, MD, PhD
      • Heidelberg, Германия, 69120
        • Рекрутинг
        • Universitätsklinik Heidelberg
        • Главный следователь:
          • Antje Wick, MD
        • Контакт:
      • Mannheim, Германия, 68167
        • Рекрутинг
        • Universitaetsklinikum Heidelberg - Neurologische Klinik
        • Главный следователь:
          • Michael Platten, MD
        • Контакт:
          • Yvonne Neu
          • Номер телефона: +49 621 383-6801
          • Электронная почта: yvonne.neu@umm.de
      • Regensburg, Германия, 93053
        • Рекрутинг
        • Universitätsklinikum Regensburg
        • Главный следователь:
          • Peter Hau, MD
        • Контакт:
          • Peter Hau, MD
          • Номер телефона: +49 (0)941 941-8083
          • Электронная почта: Peter.Hau@ukr.de
      • Tübingen, Германия, 72076
        • Рекрутинг
        • Universitätsklinikum Tübingen
        • Главный следователь:
          • Ghazaleh Tabatabai, MD
        • Контакт:
  • Канада
    • Ontario
      • Toronto, Ontario, Канада, M4N 3M5
        • Рекрутинг
        • Sunnybrook Health Sciences Centre
        • Контакт:
        • Главный следователь:
          • James Perry, MD, FRCPC
        • Контакт:
      • Toronto, Ontario, Канада, M5G 2C1
        • Рекрутинг
        • Princess Margaret Cancer Centre
        • Главный следователь:
          • Warren Mason, MD
        • Контакт:
          • On Yee Jones, RN
          • Номер телефона: 4603 416-946-4501
          • Электронная почта: onyee.jones@uhn.ca
        • Контакт:
          • Tenzin Yangdol
          • Номер телефона: 4624 416-946-4501
          • Электронная почта: Tenzin.Yangdol@uhn.ca
    • Quebec
      • Montreal, Quebec, Канада, H3A 2B4
        • Активный, не рекрутирующий
        • Montreal Neurological Institute and Hospital, McGill University
      • Sherbrooke, Quebec, Канада, J1H 5H3
        • Активный, не рекрутирующий
        • Université de Sherbrooke
  • Соединенные Штаты
    • Alabama
      • Birmingham, Alabama, Соединенные Штаты, 35249
        • Рекрутинг
        • University of Alabama at Birmingham
        • Главный следователь:
          • Louis B Nabors, MD
        • Контакт:
          • Thiru Pillay
          • Номер телефона: 205-934-1432
          • Электронная почта: Tpillay@uabmc.edu
        • Контакт:
          • Yantong (Lily) Liu
          • Номер телефона: 205-975-2283
          • Электронная почта: yantongliu@uabmc.edu
    • California
      • La Jolla, California, Соединенные Штаты, 92093
        • Рекрутинг
        • University of California, San Diego
        • Главный следователь:
          • David Piccioni, MD, PhD
        • Контакт:
        • Контакт:
      • Los Angeles, California, Соединенные Штаты, 90048
        • Активный, не рекрутирующий
        • Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
      • Los Angeles, California, Соединенные Штаты, 90095
        • Активный, не рекрутирующий
        • University of California, Los Angeles
      • Orange, California, Соединенные Штаты, 92868
        • Рекрутинг
        • St. Joseph Hospital
        • Главный следователь:
          • Lars Anker, MD
        • Контакт:
      • San Francisco, California, Соединенные Штаты, 94143
        • Рекрутинг
        • University of California, San Francisco
        • Главный следователь:
          • Nicholas Butowski, MD
        • Контакт:
      • Stanford, California, Соединенные Штаты, 94305
        • Завершенный
        • Stanford Cancer Center
    • Colorado
      • Aurora, Colorado, Соединенные Штаты, 80045
        • Рекрутинг
        • University of Colorado Denver
        • Главный следователь:
          • Denise Damek, MD
        • Контакт:
    • Connecticut
      • New Haven, Connecticut, Соединенные Штаты, 06511
        • Рекрутинг
        • Yale Cancer Center / Smilow Cancer Hospital*
        • Главный следователь:
          • Nicholas Blondin, MD
        • Контакт:
          • Amy L. Rodrigues
          • Номер телефона: 203-785-5702
          • Электронная почта: Amy.rodrigues@yale.edu
    • Florida
      • Jacksonville, Florida, Соединенные Штаты, 32224
        • Завершенный
        • Mayo Clinic Cancer Center
      • Miami, Florida, Соединенные Штаты, 33136
        • Рекрутинг
        • Sylvester Comprehensive Cancer Center*
        • Главный следователь:
          • Macarena I De La Fuente, MD
        • Контакт:
          • Leonela Wright
          • Номер телефона: 305-243-0864
          • Электронная почта: lxw612@med.miami.edu
      • Tampa, Florida, Соединенные Штаты, 33612
        • Рекрутинг
        • Moffitt Cancer Center
        • Главный следователь:
          • Patrick Grogan, MD
        • Контакт:
        • Контакт:
    • Georgia
      • Atlanta, Georgia, Соединенные Штаты, 30309
        • Активный, не рекрутирующий
        • Piedmont Atlanta Hospital
      • Atlanta, Georgia, Соединенные Штаты, 30322
        • Активный, не рекрутирующий
        • Winship Cancer Institute of Emory University
    • Louisiana
      • New Orleans, Louisiana, Соединенные Штаты, 70112
        • Завершенный
        • LSU Health Sciences Center - New Orleans
    • Massachusetts
      • Boston, Massachusetts, Соединенные Штаты, 02114
        • Рекрутинг
        • Massachusetts General Hospital
        • Главный следователь:
          • Patrick Wen, MD
        • Контакт:
          • Patrick Wen, MD
          • Номер телефона: 617-726-5130
          • Электронная почта: pwen@mgb.org
      • Boston, Massachusetts, Соединенные Штаты, 02115
        • Рекрутинг
        • Dana Farber Cancer Institute
        • Контакт:
        • Контакт:
        • Главный следователь:
          • Laxmi Nayak, MD
    • Michigan
      • Detroit, Michigan, Соединенные Штаты, 48202
        • Завершенный
        • Henry Ford Health System
    • Minnesota
      • Minneapolis, Minnesota, Соединенные Штаты, 55407
        • Рекрутинг
        • Allina Health Systems/Abbott Northwestern Hospital
        • Главный следователь:
          • Andrea Wasilewski, MD
        • Контакт:
      • Rochester, Minnesota, Соединенные Штаты, 55905
        • Завершенный
        • Mayo Clinic Cancer Center - Rochester
    • Mississippi
      • Jackson, Mississippi, Соединенные Штаты, 39213
        • Завершенный
        • University of Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, Соединенные Штаты, 63110
        • Завершенный
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • New York, New York, Соединенные Штаты, 10032
        • Рекрутинг
        • Columbia University Medical Center
        • Главный следователь:
          • Andrew Lassman, MD
        • Контакт:
      • New York, New York, Соединенные Штаты, 10016
        • Активный, не рекрутирующий
        • Perlmutter Cancer Center, NYU Langone Health
      • New York, New York, Соединенные Штаты, 10029
        • Активный, не рекрутирующий
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, Соединенные Штаты, 10065
        • Рекрутинг
        • Memorial Sloan Kettering Cancer Center*
        • Главный следователь:
          • Ingo Mellinghoff, MD
        • Контакт:
          • Kerina Yang
          • Номер телефона: 901-883-0840
          • Электронная почта: yangk3@mskcc.org
        • Контакт:
          • Nancy Keith
          • Номер телефона: 646-300-0216
          • Электронная почта: KeithN@mskcc.org
    • North Carolina
      • Durham, North Carolina, Соединенные Штаты, 27710
        • Активный, не рекрутирующий
        • Duke University Medical Center
      • Winston-Salem, North Carolina, Соединенные Штаты, 272157
        • Рекрутинг
        • Comprehensive Cancer Center of Wake Forest*
        • Главный следователь:
          • Glenn Lesser, MD
        • Контакт:
    • Ohio
      • Cleveland, Ohio, Соединенные Штаты, 44195
        • Рекрутинг
        • Cleveland Clinic
        • Главный следователь:
          • Mina Lobbous, MD
        • Контакт:
          • Kathy Robinson
          • Номер телефона: 216-444-8923
          • Электронная почта: robinsk2@ccf.org
        • Контакт:
          • Rachel Hufsey
          • Номер телефона: 216-442-6671
          • Электронная почта: HUFSEYR@ccf.org
      • Cleveland, Ohio, Соединенные Штаты, 44106
        • Рекрутинг
        • University Hospitals Cleveland Medical Center*
        • Главный следователь:
          • Herbert Newton, MD
        • Контакт:
        • Контакт:
      • Columbus, Ohio, Соединенные Штаты, 43210
        • Активный, не рекрутирующий
        • Ohio State University Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Соединенные Штаты, 19104
        • Активный, не рекрутирующий
        • University of Pennsylvania - Perelman Center for Advanced Medicine
      • Pittsburgh, Pennsylvania, Соединенные Штаты, 15232
        • Активный, не рекрутирующий
        • University of Pittsburgh Medical Center - Hillman Cancer Center
      • Pittsburgh, Pennsylvania, Соединенные Штаты, 15212
        • Завершенный
        • Allegheny General Hospital
    • South Carolina
      • Charleston, South Carolina, Соединенные Штаты, 29425
        • Рекрутинг
        • Medical University of South Carolina - Hollings Cancer Center
        • Главный следователь:
          • Scott Lindhorst, MD
        • Контакт:
    • Texas
      • Austin, Texas, Соединенные Штаты, 78705
        • Активный, не рекрутирующий
        • Texas Oncology - Austin
      • Dallas, Texas, Соединенные Штаты, 75390
        • Активный, не рекрутирующий
        • University of Texas Southwestern Medical Center
      • Houston, Texas, Соединенные Штаты, 77030
        • Активный, не рекрутирующий
        • University of Texas - MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, Соединенные Штаты, 84112
        • Рекрутинг
        • University of Utah - Huntsman Cancer Institute
        • Главный следователь:
          • Howard Colman, MD, PhD
        • Контакт:
          • Yuri Kida
          • Номер телефона: 801-646-4397
          • Электронная почта: yuri.kida@hci.utah.edu
        • Контакт:
    • Virginia
      • Charlottesville, Virginia, Соединенные Штаты, 22908
        • Рекрутинг
        • University of Virginia Health
        • Контакт:
          • CJ Woodburn
          • Номер телефона: 434-243-9900
          • Электронная почта: cjw4v@virginia.edu
        • Главный следователь:
          • David Schiff, MD
    • Washington
      • Seattle, Washington, Соединенные Штаты, 98101
        • Активный, не рекрутирующий
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, Соединенные Штаты, 53226
        • Рекрутинг
        • Froedtert Hospital/Medical College of Wisconsin
        • Главный следователь:
          • Jennifer Connelly, MD
        • Контакт:
          • Chris Fueger
          • Номер телефона: 414-805-8837
          • Электронная почта: cfueger@mcw.edu
        • Контакт:
          • Bailee Fritz
          • Номер телефона: 414-805-8939
          • Электронная почта: bfritz@mcw.edu
  • Франция
      • Bron, Франция, 69677
        • Рекрутинг
        • Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
        • Главный следователь:
          • Francois Ducray, MD
        • Контакт:
      • Marseille, Франция, 13005
        • Рекрутинг
        • Hopital de la Timone
        • Контакт:
          • Didier Autran
          • Номер телефона: +334 91 3848 34
          • Электронная почта: didier.autran@ap-hm.fr
        • Главный следователь:
          • Emelie Tabouret, MD
      • Paris, Франция, 75013
        • Рекрутинг
        • Hopital Piti-Salpetriere
        • Контакт:
          • Mehdi Touat, MD
          • Номер телефона: +33 (0)1 42 16 03 81
          • Электронная почта: mehdi.touat@ahph.fr
        • Главный следователь:
          • Mehdi Touat, MD
  • Швейцария
      • Zurich, Швейцария
        • Рекрутинг
        • University Hospital Zurich
        • Главный следователь:
          • Michael Weller, MD
        • Контакт:
          • Номер телефона: +41 44 255 55 11
          • Электронная почта: neurologie@usz.ch
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Швейцария, 1011
        • Рекрутинг
        • Centre Hospitalier Universitaire Vaudois Lausanne
        • Главный следователь:
          • Andreas Hottinger, MD
        • Контакт:
          • Andreas Hottinger, MD
          • Номер телефона: +41 79 556 97 74
          • Электронная почта: Andreas.Hottinger@chuv.ch

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Последовательное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Активный компаратор: 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.
Лекарство: Temozolomide

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

Другие имена:
  • Темодар
  • Темодал
  • Темкад
Лекарство: Lomustine

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

Другие имена:
  • CCNU
  • CeeNU
  • Глеостин
Радиация: Radiation

60 Gy
Экспериментальный: 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).
Лекарство: 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)

Другие имена:
  • ЗАЛИВ 73-4506
  • Стиварга
Экспериментальный: 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.
Лекарство: 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

Другие имена:
  • ГДК-0084
Экспериментальный: 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.
Лекарство: 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.

Другие имена:
  • Диангидрогалактитол
Экспериментальный: 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.
Лекарство: 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.
Экспериментальный: 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.
Лекарство: 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.
Экспериментальный: 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.
Лекарство: 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.
Экспериментальный: 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.
Лекарство: Troriluzole

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

Другие имена:
  • БХВ-4157
Экспериментальный: 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.
Лекарство: Troriluzole

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

Другие имена:
  • БХВ-4157
Экспериментальный: 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.
Лекарство: Troriluzole

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

Другие имена:
  • БХВ-4157
Экспериментальный: 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.
Биологический: 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

Другие имена:
  • Пегаргиминаза
Экспериментальный: 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.
Биологический: 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

Другие имена:
  • Пегаргиминаза
Экспериментальный: 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.
Биологический: 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

Другие имена:
  • Пегаргиминаза
Экспериментальный: 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.
Лекарство: AZD1390

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

Другие имена:
  • ЭДО-С101
Экспериментальный: 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.
Лекарство: 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.

Другие имена:
  • ЭДО-С101
Экспериментальный: 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.
Лекарство: 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.

Другие имена:
  • ЭДО-С101

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Overall Survival (OS)
Временное ограничение: 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.

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Progression-free survival (PFS)
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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.

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Global Coalition for Adaptive Research

Соавторы

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

Следователи

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

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Полезные ссылки

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

30 июля 2019 г.

Первичное завершение (Оцененный)

1 июня 2028 г.

Завершение исследования (Оцененный)

1 июня 2030 г.

Даты регистрации исследования

Первый отправленный

23 мая 2019 г.

Впервые представлено, что соответствует критериям контроля качества

30 мая 2019 г.

Первый опубликованный (Действительный)

31 мая 2019 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

2 ноября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

29 октября 2026 г.

Последняя проверка

1 июня 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • GCAR-7213

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

НЕ РЕШЕНО

Описание плана IPD

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

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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