A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma

NCT03970447 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GCAR-7213
• Study Type: interventional
• Target: 2,250
• Locations: 6 countries
• Sites: 63

Brief Summary

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.

Conditions

Glioblastoma

Keywords

Glioblastoma; Newly diagnosed; recurrent; O6-methylguanine-DNA-methyltransferase (MGMT) methylated; MGMT unmethylated; isocitrate dehydrogenase (IDH) wild-type; Bayesian; adaptive randomization; Master Protocol; Platform Trial; Phase 2; Phase 3

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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.

Secondary Outcomes (3)

• Progression-free survival (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

  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)

  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.

Study Arms (17)

Control Arm

ACTIVE COMPARATOR

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.

Drug: Temozolomide; Drug: Lomustine; Radiation: Radiation

Regorafenib Treatment Arm- Enrollment concluded

EXPERIMENTAL

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).

Drug: Regorafenib

Paxalisib Treatment Arm- Enrollment concluded

EXPERIMENTAL

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.

Drug: Paxalisib

VAL-083 Treatment Arm- Enrollment concluded

EXPERIMENTAL

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.

Drug: VAL-083

VT1021 Treatment Arm - Dose Finding Phase

EXPERIMENTAL

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.

Drug: VT1021

VT1021 Treatment Arm - Enhanced Safety Management (ESM)

EXPERIMENTAL

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.

Drug: VT1021

VT1021 Treatment Arm

EXPERIMENTAL

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.

Drug: VT1021

Troriluzole Treatment Arm - Dose Finding Phase

EXPERIMENTAL

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.

Drug: Troriluzole

Troriluzole Treatment Arm - Enhanced Safety Management (ESM)

EXPERIMENTAL

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.

Drug: Troriluzole

Troriluzole Treatment Arm

EXPERIMENTAL

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.

Drug: Troriluzole

ADI-PEG 20 Treatment Arm - Dose Finding Phase

EXPERIMENTAL

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.

Biological: ADI-PEG 20

ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM)

EXPERIMENTAL

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.

Biological: ADI-PEG 20

ADI-PEG 20 Treatment Arm

EXPERIMENTAL

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.

Biological: ADI-PEG 20

AZD1390 Treatment Arm

EXPERIMENTAL

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.

Drug: AZD1390

Tinostamustine - Dose finding phase

EXPERIMENTAL

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).

Drug: Tinostamustine

Tinostamustine - Enhanced Safety Management

EXPERIMENTAL

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.

Drug: Tinostamustine

Investigation arm: Tinostamustine

EXPERIMENTAL

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.

Drug: Tinostamustine

Interventions

Tinostamustine DRUG

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.

Also known as: EDO-S101

Investigation arm: Tinostamustine; Tinostamustine - Dose finding phase; Tinostamustine - Enhanced Safety Management

Temozolomide DRUG

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

Also known as: Temodar, Temodal, Temcad

Control Arm

Lomustine DRUG

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

Also known as: CCNU, CeeNU, Gleostine

Control Arm

Regorafenib DRUG

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)

Also known as: Stivarga, BAY 73-4506

Regorafenib Treatment Arm- Enrollment concluded

Radiation RADIATION

60 Gy

Control Arm

Paxalisib DRUG

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

Also known as: GDC-0084

Paxalisib Treatment Arm- Enrollment concluded

VAL-083 DRUG

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.

Also known as: Dianhydrogalactitol

VAL-083 Treatment Arm- Enrollment concluded

VT1021 DRUG

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.

VT1021 Treatment Arm; VT1021 Treatment Arm - Dose Finding Phase; VT1021 Treatment Arm - Enhanced Safety Management (ESM)

Troriluzole DRUG

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

Also known as: BHV-4157

Troriluzole Treatment Arm; Troriluzole Treatment Arm - Dose Finding Phase; Troriluzole Treatment Arm - Enhanced Safety Management (ESM)

ADI-PEG 20 BIOLOGICAL

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

Also known as: Pegargiminase

ADI-PEG 20 Treatment Arm; ADI-PEG 20 Treatment Arm - Dose Finding Phase; ADI-PEG 20 Treatment Arm - Enhanced Safety Management (ESM)

AZD1390 DRUG

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

AZD1390 Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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, and 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.

Sponsors & Collaborators

• Biohaven Pharmaceuticals, Inc.: collaborator
• Vigeo Therapeutics, Inc.: collaborator
• AstraZeneca: collaborator
• Imbrium Therapeutics: collaborator
• Global Coalition for Adaptive Research: lead
• Bayer: collaborator
• Kazia Therapeutics Limited: collaborator
• Kintara Therapeutics, Inc.: collaborator
• Polaris Group: collaborator

Study Sites (63)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

RECRUITING

University of California, San Diego

La Jolla, California, 92093, United States

RECRUITING

Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

RECRUITING

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

St. Joseph Hospital

Orange, California, 92868, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Stanford Cancer Center

Stanford, California, 94305, United States

COMPLETED

University of Colorado Denver

Aurora, Colorado, 80045, United States

RECRUITING

Yale Cancer Center / Smilow Cancer Hospital

New Haven, Connecticut, 06511, United States

RECRUITING

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

COMPLETED

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

COMPLETED

LSU Health Sciences Center - New Orleans

New Orleans, Louisiana, 70112, United States

ACTIVE NOT RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

ACTIVE NOT RECRUITING

Allina Health Systems/Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

RECRUITING

Mayo Clinic Cancer Center - Rochester

Rochester, Minnesota, 55905, United States

COMPLETED

University of Mississippi Medical Center

Jackson, Mississippi, 39213, United States

COMPLETED

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

COMPLETED

Perlmutter Cancer Center, NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Comprehensive Cancer Center of Wake Forest

Winston-Salem, North Carolina, 272157, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Ohio State University Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Pennsylvania - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

ACTIVE NOT RECRUITING

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Medical University of South Carolina - Hollings Cancer Center

Charleston, South Carolina, 29425, United States

RECRUITING

Texas Oncology - Austin

Austin, Texas, 78705, United States

ACTIVE NOT RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

ACTIVE NOT RECRUITING

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Utah - Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

University of Virginia Health

Charlottesville, Virginia, 22908, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98101, United States

ACTIVE NOT RECRUITING

Froedtert Hospital/Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

ACTIVE NOT RECRUITING

Northern Sydney Cancer Centre/Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

RECRUITING

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

RECRUITING

Austin Health

Heidelberg, Victoria, 3084, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

RECRUITING

Montreal Neurological Institute and Hospital, McGill University

Montreal, Quebec, H3A 2B4, Canada

RECRUITING

Université de Sherbrooke

Sherbrooke, Quebec, J1H 5H3, Canada

ACTIVE NOT RECRUITING

Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer

Bron, 69677, France

RECRUITING

Hopital de la Timone

Marseille, 13005, France

RECRUITING

Hopital Piti-Salpetriere

Paris, 75013, France

RECRUITING

Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie

Cologne, 50937, Germany

ACTIVE NOT RECRUITING

Dr. Senckenbergisches Institut für Neuroonkologie

Frankfurt, 60528, Germany

RECRUITING

Universitätsklinik Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitaetsklinikum Heidelberg - Neurologische Klinik

Mannheim, 68167, Germany

RECRUITING

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

Centre Hospitalier Universitaire Vaudois Lausanne

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

University Hospital Zurich

Zurich, Switzerland

RECRUITING

Related Publications (2)

• Wen PY, Berry DA, Buxton MB, Colman H, de Groot J, Lim M, Mellinghoff I, Perry JR, Weller M, Blondin NA, Butt OH, Damek DM, de la Fuente MI, Drappatz J, Dunbar E, Giglio P, Hyddmark EV, Iwamoto F, Jaeckle KA, Kim L, Kling HM, Lee EQ, Mantica M, Mikkelsen T, Nabors B, Newton HB, Olson JJ, Schiff D, Walbert T, Weathers SP, Cloughesy T, Lassman AB; GBM AGILE Regorafenib Study Group. Evaluation of Regorafenib in Newly Diagnosed and Recurrent Glioblastoma: GBM AGILE Phase II/III Bayesian Randomized Platform Trial. J Clin Oncol. 2026 Apr 14:JCO2501137. doi: 10.1200/JCO-25-01137. Online ahead of print.

  PMID: 41980234 DERIVED

• Chen JJ, Vincent MY, Shepard D, Peereboom D, Mahalingam D, Battiste J, Patel MR, Juric D, Wen PY, Bullock A, Selfridge JE, Pant S, Liu J, Li W, Fyfe S, Wang S, Zota V, Mahoney J, Watnick RS, Cieslewicz M, Watnick J. Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors. Commun Med (Lond). 2024 May 21;4(1):95. doi: 10.1038/s43856-024-00520-z.

  PMID: 38773224 DERIVED

Related Links

• Global Coalition for Adaptive Research Website

MeSH Terms

Conditions

Glioblastoma; Recurrence

Interventions

Temozolomide; Lomustine; regorafenib; Radiation; GDC-0084; Dianhydrogalactitol; ADI PEG20; AZD1390; tinostamustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Physical Phenomena; Galactitol; Sugar Alcohols; Alcohols; Carbohydrates

Study Officials

• Tim Cloughesy, MD

  GCAR CMO and GBM AGILE Global PI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patient Information

CONTACT

310-598-3199; patientinfo@gcaresearch.org

Rachel Rosenstein-Sisson

CONTACT

RRosenstein.Sisson@GCAResearch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: GBM AGILE is a multi-arm, platform trial. The evaluation of each therapy in GBM AGILE may proceed in 2 possible stages. Stage 1 is an adaptively randomized Screening stage for evaluating the therapy within patient signatures compared against a common control. A therapy in Stage 1 will stop accruing patients if it reaches its maximal sample size, drops for limited efficacy, or evinces inadequate safety. If a therapy reaches an efficacy threshold for continuation from Stage 1, it will move into Stage 2 within one of the prospectively defined signatures. The maximum sample size in Stage 1 is 200 patients. For a therapy moving to Stage 2 there is a fixed randomization, expansion cohort. The maximum sample size in Stage 2 is 50 experimental patients in the continued signature. The primary analysis of a regimen's effect on OS uses all patients in both its stages and all control patients in the trial in the continued signature, suitability adjusted for any possible time trends.

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: May 31, 2019
• Study Start: July 30, 2019
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

AU (6); CH (2); CA (4); US (42); FR (3); DE (6)