A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (GBM AGILE)

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ClinicalTrials.gov Identifier: NCT03970447

Recruitment Status : Recruiting

First Posted : May 31, 2019

Last Update Posted : April 29, 2024

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View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

Bayer

Kazia Therapeutics Limited

Kintara Therapeutics, Inc.

Biohaven Pharmaceuticals, Inc.

Vigeo Therapeutics, Inc.

Polaris Group

Information provided by (Responsible Party):

Global Coalition for Adaptive Research

Study Description

Brief Summary:

Condition or disease	Intervention/treatment	Phase
Glioblastoma	Drug: Temozolomide Drug: Lomustine Drug: Regorafenib Radiation: Radiation Drug: Paxalisib Drug: VAL-083 Drug: VT1021 Drug: Troriluzole Biological: ADI-PEG 20	Phase 2 Phase 3

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1030 participants
Allocation:	Randomized
Intervention Model:	Sequential Assignment
Intervention Model Description:	GBM AGILE is a multi-arm, platform trial. The evaluation of each therapy in GBM AGILE proceeds in 2 possible stages. A therapy's 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 futility, or evinces inadequate safety. If a therapy reaches an efficacy threshold for graduation from Stage 1, it will move into Stage 2 within one of the prospectively defined signatures. The maximum sample size in Stage 1 is 150 patients. For a therapy graduating to Stage 2 there is a fixed randomization, expansion cohort. The maximum sample size in Stage 2 is 50 experimental patients in the graduating 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 graduating signature, suitably adjusted for any possible time trends.
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	July 30, 2019
Estimated Primary Completion Date :	June 2026
Estimated Study Completion Date :	June 2028

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Temozolomide Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg Other Names: Temodar Temodal Temcad Drug: Lomustine Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg Other Names: CCNU CeeNU Gleostine Radiation: Radiation 60 Gy
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).	Drug: 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) Other Names: Stivarga BAY 73-4506
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.	Drug: 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 Other Name: GDC-0084
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.	Drug: 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. Other Name: Dianhydrogalactitol
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.	Drug: 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.
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.	Drug: 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.
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 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 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.
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.	Drug: Troriluzole Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID. Other Name: BHV-4157
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.	Drug: Troriluzole Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID. Other Name: BHV-4157
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 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 Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID. Other Name: BHV-4157
Experimental: 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.	Biological: 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 Other Name: Pegargiminase
Experimental: 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.	Biological: 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 Other Name: Pegargiminase
Experimental: 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.	Biological: 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 Other Name: Pegargiminase

Outcome Measures

Primary Outcome Measures :

Overall Survival (OS) [ Time Frame: 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.

Secondary Outcome Measures :

Progression-free survival (PFS) [ Time Frame: 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.
Tumor Response [ Time Frame: 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.
Duration of Response (CR + PR) [ Time Frame: 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.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 > 450 msec if male and QTc > 470 msec if female.
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, 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 > 450 msec if male and QTc > 470 msec if female.
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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03970447

Contacts

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Contact: Patient Information	310-598-3199	patientinfo@gcaresearch.org
Contact: Rachel Rosenstein-Sisson		RRosenstein.Sisson@GCAResearch.org

Locations

Show 61 study locations

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United States, Alabama
University of Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35249
Contact: Shirley Gibbs 205-975-0447 sgibbs@uab.edu
Principal Investigator: Louis B Nabors, MD
United States, California
University of California, San Diego	Recruiting
La Jolla, California, United States, 92093
Contact: Sheila Medina-Torne 858-822-1847 s4medina@health.ucsd.edu
Principal Investigator: David Piccioni, MD, PhD
Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute	Active, not recruiting
Los Angeles, California, United States, 90048
University of California, Los Angeles	Recruiting
Los Angeles, California, United States, 90095
Contact: Emy Filka 310-794-3521 efilka@mednet.ucla.edu
Principal Investigator: Phioanh Nghiemphu, MD
St. Joseph Hospital	Recruiting
Orange, California, United States, 92868
Contact: Christine Lichti 714-714-6220 Christine.lichti@stjoe.org
Principal Investigator: Lars Anker, MD
University of California, San Francisco	Active, not recruiting
San Francisco, California, United States, 94143
Stanford Cancer Center	Active, not recruiting
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Denver	Recruiting
Aurora, Colorado, United States, 80045
Contact: Julie Compton 720-848-8312 Julie.Compton@cuanschutz.edu
Principal Investigator: Denise Damek, MD
United States, Connecticut
Yale Cancer Center / Smilow Cancer Hospital	Recruiting
New Haven, Connecticut, United States, 06511
Contact: Phyllis Nortey 203-737-1881 phyllis.nortey@yale.edu
Principal Investigator: Nicholas Blondin, MD
United States, Florida
Mayo Clinic Cancer Center	Active, not recruiting
Jacksonville, Florida, United States, 32224
Sylvester Comprehensive Cancer Center	Recruiting
Miami, Florida, United States, 33136
Contact: Yaima de la Fuente 305-243-5189 Yaima.delaFuente@med.miami.edu
Principal Investigator: Macarena I De La Fuente, MD
Moffitt Cancer Center	Recruiting
Tampa, Florida, United States, 33612
Contact: Sebastian Matzza 813-745-1158 sebastian.matzza@moffitt.org
Principal Investigator: Patrick Grogan, MD
United States, Georgia
Piedmont Atlanta Hospital	Recruiting
Atlanta, Georgia, United States, 30309
Contact: Ali Arabnia 404-425-7943 Ali.arabnia@piedmont.org
Contact: Dionne Jean 404-425-7927 dionne.jean@Piedmont.org
Principal Investigator: Erin Dunbar, MD
Winship Cancer Institute of Emory University	Active, not recruiting
Atlanta, Georgia, United States, 30322
United States, Louisiana
LSU Health Sciences Center - New Orleans	Active, not recruiting
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Lauren Hibyan 617-643-8992 lmhibyan@partners.org
Contact: Marie Aste 617-724-2262 maste@partners.org
Principal Investigator: Patrick Wen, MD
Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jennifer Borowka 617-632-2166 Jennifer_Borowka@DFCI.HARVARD.EDU
Principal Investigator: Patrick Wen, MD
United States, Michigan
Henry Ford Health System	Active, not recruiting
Detroit, Michigan, United States, 48202
United States, Minnesota
Abbott Northwestern Hospital	Recruiting
Minneapolis, Minnesota, United States, 55407
Contact 612-863-3452 neurooncologyresearch@allina.com
Principal Investigator: Andrea Wasilewski, MD
Mayo Clinic Cancer Center - Rochester	Active, not recruiting
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center	Active, not recruiting
Jackson, Mississippi, United States, 39213
United States, Missouri
Washington University School of Medicine - Siteman Cancer Center	Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Perlmutter Cancer Center, NYU Langone Health	Recruiting
New York, New York, United States, 10016
Contact: Julia Payne 917-907-0870 Julia.Payne@nyulangone.org
Principal Investigator: Erik Sulman, MD, PhD
Icahn School of Medicine at Mount Sinai	Recruiting
New York, New York, United States, 10029
Contact: Suzette Days-Mays 646-531-4350 suzette.dayes-mays@mountsinai.org
Principal Investigator: Lyndon Kim, MD
Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Alicia Bargo 212-342-4435 ab5172@cumc.columbia.edu
Contact: Denisse Torres 212-304-6329 dt2684@cumc.columbia.edu
Principal Investigator: Andrew Lassman, MD
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Lindsey Myers 917-453-2968 MyersL1@mskcc.org
Principal Investigator: Ingo Mellinghoff, MD
United States, North Carolina
Duke University Medical Center	Active, not recruiting
Durham, North Carolina, United States, 27710
Comprehensive Cancer Center of Wake Forest	Recruiting
Winston-Salem, North Carolina, United States, 272157
Contact: Ashley Fansler 336-713-3551 arcarroll@wakehealth.edu
Contact: James Morgan 336-712-4491 jwmorgan@wakehealth.edu
Principal Investigator: Glenn Lesser, MD
United States, Ohio
University Hospitals Cleveland Medical Center	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Melissa Brately melissa.brately@UHhospitals.org
Contact: Carmen Gray carmen.gray@UHhospitals.org
Principal Investigator: Herbert Newton, MD
Cleveland Clinic	Active, not recruiting
Cleveland, Ohio, United States, 44195
Ohio State University Cancer Center	Active, not recruiting
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania - Perelman Center for Advanced Medicine	Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
Allegheny General Hospital	Active, not recruiting
Pittsburgh, Pennsylvania, United States, 15212
University of Pittsburgh Medical Center - Hillman Cancer Center	Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Tyler Boyce 412-623-3962 boycet@upmc.edu
Principal Investigator: Jan Drappatz, MD
United States, South Carolina
Medical University of South Carolina - Hollings Cancer Center	Recruiting
Charleston, South Carolina, United States, 29425
Contact: Jennifer Kinsey 843-792-1484 kinsejen@musc.edu
Principal Investigator: Scott Lindhorst, MD
United States, Texas
Texas Oncology - Austin	Recruiting
Austin, Texas, United States, 78705
Contact: Michelle Owens 512-421-4234 michelle.owens@usoncology.com
Principal Investigator: Andrew Brenner, MD
University of Texas Southwestern Medical Center	Active, not recruiting
Dallas, Texas, United States, 75390
University of Texas - MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Evguenia Gachimova, RN 832-266-3519 EGachimova@mdanderson.org
Principal Investigator: Shiao-Pei Weathers, MD
United States, Utah
University of Utah - Huntsman Cancer Institute	Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Rachel Kingsford 801-585-0550 rachel.kingsford@hci.utah.edu
Contact: Yuri Kida 801-646-4397 yuri.kida@hci.utah.edu
Principal Investigator: Howard Colman, MD, PhD
United States, Virginia
University of Virginia Health	Recruiting
Charlottesville, Virginia, United States, 22908
Contact: CJ Woodburn 434-243-9900 cjw4v@virginia.edu
Principal Investigator: David Schiff, MD
United States, Washington
University of Washington Medical Center	Active, not recruiting
Seattle, Washington, United States, 98101
United States, Wisconsin
Froedtert Hospital/Medical College of Wisconsin	Active, not recruiting
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Northern Sydney Cancer Centre/Royal North Shore Hospital	Recruiting
St Leonards, New South Wales, Australia, 2065
Contact: Daisy Yu (02) 9463 1217 wenqiong.yu@health.nsw.gov.au
Principal Investigator: Helen Wheeler, MD
Calvary Mater Newcastle	Recruiting
Waratah, New South Wales, Australia, 2298
Contact: Kim Adler +61 (0)2 40143282 kim.adler@calvarymater.org.au
Principal Investigator: James Lynam, MD
Australia, Victoria
Austin Health	Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Samantha Chakar (03) 9496 3088 samantha.chakar@austin.org.au
Principal Investigator: Hui Gan, MBBS, FRACP, PhD
Peter MacCallum Cancer Centre	Recruiting
Melbourne, Victoria, Australia
Contact: Richelle Linklater Richelle.Linklater@petermac.org
Principal Investigator: Mark Rosenthal, Prof.
Principal Investigator: Jim Whittle, MD
Canada, Ontario
Sunnybrook Health Sciences Centre	Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Delareese Mackenzie 416-480-5000 ext 7362 delareese.mackenzie@sunnybrook.ca
Principal Investigator: James Perry, MD, FRCPC
Princess Margaret Cancer Centre	Recruiting
Toronto, Ontario, Canada, M5G 2C1
Contact: Rhema Babyson, MSc 416-946-4501 ext 5993 rhema.babyson@uhn.ca
Principal Investigator: Warren Mason, MD
Canada, Quebec
Montreal Neurological Institute and Hospital, McGill University	Recruiting
Montréal, Quebec, Canada, H3A 2B4
Contact: Gabriele Riva 514-398-6907 gabriele.riva@mcgill.ca
Principal Investigator: Scott Owen, MD
Université de Sherbrooke	Active, not recruiting
Sherbrooke, Quebec, Canada, J1H 5H3
France
Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer	Recruiting
Bron, France, 69677
Contact: Apolline Barthelme 00 33 4 26 73 97 87 apolline.barthelme@chu-lyon.fr
Principal Investigator: Francois Ducray, MD
Hopital de la Timone	Recruiting
Marseille, France, 13005
Contact: Didier Autran +334 91 3848 34 didier.autran@ap-hm.fr
Principal Investigator: Olivier Chinot, MD
Hopital Piti-Salpetriere	Recruiting
Paris, France, 75013
Contact: Mehdi Touat, MD +33 (0)1 42 16 03 81 mehdi.touat@ahph.fr
Principal Investigator: Mehdi Touat, MD
Germany
Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie	Recruiting
Cologne, Germany, 50937
Contact: Norbert Galldiks +49-221-478-86124 norbert.galldiks@uk-koeln.de
Principal Investigator: Norbert Galldiks, Prof.
Dr. Senckenbergisches Institut für Neuroonkologie	Recruiting
Frankfurt, Germany, 60528
Contact: Michael Ronellenfitsch, MD,PhD +49(0)69 6301 87711 m.ronellenfitsch@med.uni-frankfurt.de
Principal Investigator: Michael Ronellenfitsch, MD, PhD
Universitätsklinik Heidelberg	Recruiting
Heidelberg, Germany, 69120
Contact: Antje Wick, MD +49 (0) 6221-56 ext 7075 antje.wick@med.uni-heidelberg.de
Principal Investigator: Antje Wick, MD
Universitätsklinikum Regensburg	Recruiting
Regensburg, Germany, 93053
Contact: Peter Hau, MD +49 (0)941 941-8083 Peter.Hau@ukr.de
Principal Investigator: Peter Hau, MD
Universitätsklinikum Tübingen	Recruiting
Tübingen, Germany, 72076
Contact: Ghazaleh Tabatabai +49 (0)707 12983269 Ghazaleh.Tabatabai@med.uni-tuebingen.de
Principal Investigator: Ghazaleh Tabatabai, MD
Switzerland
Centre Hospitalier Universitaire Vaudois Lausanne	Recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Andreas Hottinger, MD +41 79 556 97 74 Andreas.Hottinger@chuv.ch
Principal Investigator: Andreas Hottinger, MD
Universitätsspital Basel	Active, not recruiting
Basel, Switzerland, CH-4031
University Hospital Zurich	Recruiting
Zürich, Switzerland
Contact +41 44 255 55 11 neurologie@usz.ch
Principal Investigator: Michael Weller, MD

Sponsors and Collaborators

Global Coalition for Adaptive Research

Bayer

Kazia Therapeutics Limited

Kintara Therapeutics, Inc.

Biohaven Pharmaceuticals, Inc.

Vigeo Therapeutics, Inc.

Polaris Group

Investigators

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Principal Investigator:	Tim Cloughesy, MD	GCAR CMO and GBM AGILE Global PI

More Information

Additional Information:

Global Coalition for Adaptive Research Website This link exits the ClinicalTrials.gov site

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Responsible Party:	Global Coalition for Adaptive Research
ClinicalTrials.gov Identifier:	NCT03970447
Other Study ID Numbers:	GCAR-7213
First Posted:	May 31, 2019 Key Record Dates
Last Update Posted:	April 29, 2024
Last Verified:	April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided
Plan Description:	Global Coalition for Adaptive Research (GCAR) is in the planning stages at this time.

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Global Coalition for Adaptive Research:


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

Additional relevant MeSH terms:

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Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue	Temozolomide Lomustine Dianhydrogalactitol GDC-0084 Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors

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