A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
Study Purpose
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.
Recruitment Criteria
|
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
|
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 18 Years and Over |
| Gender | All |
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.
- - 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.
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.
Exclusion Criteria:
- - Received any prior treatment for glioma including: a.
- - 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.
Exclusion Criteria:
- - Early disease progression prior to 3 months (12 weeks) from the completion of RT.
- - More than 2 prior lines for chemotherapy administration.
- - 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.
Trial Details
|
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT03970447 |
|
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2/Phase 3 |
|
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Global Coalition for Adaptive Research |
|
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Tim Cloughesy, MD |
| Principal Investigator Affiliation | GCAR CMO and GBM AGILE Global PI |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Other, Industry |
| Overall Status | Recruiting |
| Countries | Australia, Canada, France, Germany, Switzerland, United States |
|
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Glioblastoma |
| Study Website: | View Trial Website |
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.
Arms
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 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.
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 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.
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.
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.
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.
Interventions
Drug: - Temozolomide
Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg
Drug: - Lomustine
Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg
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)
Radiation: - Radiation
60 Gy
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
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.
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.
Drug: - Troriluzole
Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.
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
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Status
Recruiting
Address
University of California, San Diego
La Jolla, California, 92093
Status
Active, not recruiting
Address
Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, 90048
Status
Recruiting
Address
University of California, Los Angeles
Los Angeles, California, 90095
Status
Recruiting
Address
St. Joseph Hospital
Orange, California, 92868
Status
Active, not recruiting
Address
University of California, San Francisco
San Francisco, California, 94143
Status
Active, not recruiting
Address
Stanford Cancer Center
Stanford, California, 94305
Status
Recruiting
Address
University of Colorado Denver
Aurora, Colorado, 80045
Status
Recruiting
Address
Yale Cancer Center / Smilow Cancer Hospital
New Haven, Connecticut, 06511
Status
Active, not recruiting
Address
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224
Status
Recruiting
Address
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Status
Recruiting
Address
Moffitt Cancer Center
Tampa, Florida, 33612
Status
Recruiting
Address
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
Status
Active, not recruiting
Address
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Status
Active, not recruiting
Address
LSU Health Sciences Center - New Orleans
New Orleans, Louisiana, 70112
Status
Recruiting
Address
Massachusetts General Hospital
Boston, Massachusetts, 02114
Status
Recruiting
Address
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Status
Active, not recruiting
Address
Henry Ford Health System
Detroit, Michigan, 48202
Status
Recruiting
Address
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55407
Status
Active, not recruiting
Address
Mayo Clinic Cancer Center - Rochester
Rochester, Minnesota, 55905
Status
Active, not recruiting
Address
University of Mississippi Medical Center
Jackson, Mississippi, 39213
Status
Active, not recruiting
Address
Washington University School of Medicine - Siteman Cancer Center
Saint Louis, Missouri, 63110
Status
Recruiting
Address
Perlmutter Cancer Center, NYU Langone Health
New York, New York, 10016
Status
Active, not recruiting
Address
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Status
Recruiting
Address
Columbia University Medical Center
New York, New York, 10032
Status
Recruiting
Address
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Status
Active, not recruiting
Address
Duke University Medical Center
Durham, North Carolina, 27710
Status
Recruiting
Address
Comprehensive Cancer Center of Wake Forest
Winston-Salem, North Carolina, 272157
Status
Recruiting
Address
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Status
Active, not recruiting
Address
Cleveland Clinic
Cleveland, Ohio, 44195
Status
Active, not recruiting
Address
Ohio State University Cancer Center
Columbus, Ohio, 43210
Status
Active, not recruiting
Address
University of Pennsylvania - Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
Status
Active, not recruiting
Address
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Status
Recruiting
Address
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Status
Recruiting
Address
Medical University of South Carolina - Hollings Cancer Center
Charleston, South Carolina, 29425
Status
Recruiting
Address
Texas Oncology - Austin
Austin, Texas, 78705
Status
Active, not recruiting
Address
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Status
Recruiting
Address
University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030
Status
Recruiting
Address
University of Utah - Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Status
Recruiting
Address
University of Virginia Health
Charlottesville, Virginia, 22908
Status
Active, not recruiting
Address
University of Washington Medical Center
Seattle, Washington, 98101
Status
Active, not recruiting
Address
Froedtert Hospital/Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
International Sites
Status
Recruiting
Address
Northern Sydney Cancer Centre/Royal North Shore Hospital
St Leonards, New South Wales, 2065
Status
Recruiting
Address
Calvary Mater Newcastle
Waratah, New South Wales, 2298
Status
Recruiting
Address
Austin Health
Heidelberg, Victoria, 3084
Status
Recruiting
Address
Peter MacCallum Cancer Centre
Melbourne, Victoria,
Status
Recruiting
Address
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Status
Recruiting
Address
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1
Status
Recruiting
Address
Montreal Neurological Institute and Hospital, McGill University
Montréal, Quebec, H3A 2B4
Status
Active, not recruiting
Address
Université de Sherbrooke
Sherbrooke, Quebec, J1H 5H3
Status
Recruiting
Address
Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer
Bron, , 69677
Status
Recruiting
Address
Hopital de la Timone
Marseille, , 13005
Status
Recruiting
Address
Hopital Piti-Salpetriere
Paris, , 75013
Status
Recruiting
Address
Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie
Cologne, , 50937
Status
Recruiting
Address
Dr. Senckenbergisches Institut für Neuroonkologie
Frankfurt, , 60528
Status
Recruiting
Address
Universitätsklinik Heidelberg
Heidelberg, , 69120
Status
Recruiting
Address
Universitätsklinikum Regensburg
Regensburg, , 93053
Status
Recruiting
Address
Universitätsklinikum Tübingen
Tübingen, , 72076
Status
Recruiting
Address
Centre Hospitalier Universitaire Vaudois Lausanne
Lausanne, Vaud, 1011
Status
Active, not recruiting
Address
Universitätsspital Basel
Basel, , CH-4031
Status
Recruiting
Address
University Hospital Zurich
Zürich, ,
