GBM AGILE: Global Adaptive Trial Master Protocol: An International, Seamless Phase II/III Response Adaptive Randomization Platform Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent GBM

Who is this study for? Patients with Glioblastoma
Status: Recruiting
Location: See all (49) locations...
Intervention Type: Drug, Radiation
Study Type: Interventional
Study Phase: Phase 2/Phase 3
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• 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.

Locations
United States
Alabama
University of Alabama at Birmingham
Recruiting
Birmingham
California
University of California, San Diego
Active, not recruiting
La Jolla
Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
Active, not recruiting
Los Angeles
University of California, Los Angeles
Recruiting
Los Angeles
St. Joseph Hospital
Active, not recruiting
Orange
University of California, San Francisco
Active, not recruiting
San Francisco
Stanford Cancer Center
Active, not recruiting
Stanford
Colorado
University of Colorado Denver
Active, not recruiting
Aurora
Connecticut
Yale Cancer Center / Smilow Cancer Hospital
Active, not recruiting
New Haven
Florida
Mayo Clinic Cancer Center
Active, not recruiting
Jacksonville
Sylvester Comprehensive Cancer Center
Active, not recruiting
Miami
Moffitt Cancer Center
Active, not recruiting
Tampa
Georgia
Piedmont Atlanta Hospital
Active, not recruiting
Atlanta
Winship Cancer Institute of Emory University
Active, not recruiting
Atlanta
Louisiana
LSU Health Sciences Center - New Orleans
Active, not recruiting
New Orleans
Massachusetts
Dana Farber Cancer Institute
Active, not recruiting
Boston
Massachusetts General Hospital
Active, not recruiting
Boston
Michigan
Henry Ford Health System
Recruiting
Detroit
Minnesota
Abbott Northwestern Hospital
Active, not recruiting
Minneapolis
Mayo Clinic Cancer Center - Rochester
Active, not recruiting
Rochester
Missouri
Washington University School of Medicine - Siteman Cancer Center
Active, not recruiting
Saint Louis
Mississippi
University of Mississippi Medical Center
Active, not recruiting
Jackson
North Carolina
Duke University Medical Center
Active, not recruiting
Durham
Comprehensive Cancer Center of Wake Forest
Active, not recruiting
Winston-salem
New York
Columbia University Medical Center
Recruiting
New York
Icahn School of Medicine at Mount Sinai
Active, not recruiting
New York
Memorial Sloan Kettering Cancer Center
Recruiting
New York
Perlmutter Cancer Center, NYU Langone Health
Active, not recruiting
New York
Ohio
Cleveland Clinic
Active, not recruiting
Cleveland
University Hospitals Cleveland Medical Center
Active, not recruiting
Cleveland
Ohio State University Cancer Center
Active, not recruiting
Columbus
Pennsylvania
University of Pennsylvania - Perelman Center for Advanced Medicine
Active, not recruiting
Philadelphia
Allegheny General Hospital
Active, not recruiting
Pittsburgh
University of Pittsburgh Medical Center - Hillman Cancer Center
Recruiting
Pittsburgh
South Carolina
Medical University of South Carolina - Hollings Cancer Center
Active, not recruiting
Charleston
Texas
Texas Oncology - Austin
Active, not recruiting
Austin
University of Texas Southwestern Medical Center
Active, not recruiting
Dallas
University of Texas - MD Anderson Cancer Center
Active, not recruiting
Houston
Utah
University of Utah - Huntsman Cancer Institute
Recruiting
Salt Lake City
Virginia
University of Virginia Health
Active, not recruiting
Charlottesville
Washington
University of Washington Medical Center
Active, not recruiting
Seattle
Wisconsin
Froedtert Hospital/Medical College of Wisconsin
Active, not recruiting
Milwaukee
Other Locations
Canada
Montreal Neurological Institute and Hospital, McGill University
Active, not recruiting
Montréal
Université de Sherbrooke
Active, not recruiting
Sherbrooke
Princess Margaret Cancer Centre
Active, not recruiting
Toronto
Sunnybrook Health Sciences Centre
Active, not recruiting
Toronto
France
Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
Active, not recruiting
Bron
Switzerland
Universitätsspital Basel
Active, not recruiting
Basel
University Hospital Zurich
Active, not recruiting
Zürich
Contact Information
Primary
Patient Information
patientinfo@gcaresearch.org
310-598-3199
Backup
Rachel Rosenstein-Sisson
RRosenstein.Sisson@GCAResearch.org
Time Frame
Start Date: July 30, 2019
Estimated Completion Date: June 2028
Participants
Target number of participants: 1030
Treatments
Active Comparator: 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.
Experimental: Regorafenib Treatment Arm
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).
Experimental: Paxalisib Treatment Arm
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.
Experimental: VAL-083 Treatment Arm
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.
Experimental: 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.
Experimental: 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.
Experimental: 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 from: 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 from: Infusion for intravenous administration; Strength: 10 mg/mL; Dose: 12mg/kg) twice weekly.
Experimental: 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.
Experimental: 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.
Experimental: 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 from: 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 from: Capsule for oral administration; Strength: 100 mg; Dose: As confirmed by dose finding phase) BID. After 6 cycles, troriluzole only.
Sponsors
Collaborators: Bayer, Vigeo Therapeutics, Inc., Kazia Therapeutics Limited, Biohaven Pharmaceuticals, Inc., Kintara Therapeutics, Inc.
Leads: Global Coalition for Adaptive Research

This content was sourced from clinicaltrials.gov

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