Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.
All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (\*).
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.
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.
Sequential
Temozolomide
DrugDosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg
Lomustine
DrugDosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg
Regorafenib
DrugDosage 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
Radiation60 Gy
Paxalisib
DrugDosage 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
VAL-083
DrugDosage 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.
VT1021
DrugDosage 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.
Troriluzole
DrugDosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.
ADI-PEG 20
Biological/VaccineDosage 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
AZD1390
DrugStandard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.
Tinostamustine
DrugDosage 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.
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Treatment groupsSee each treatment group below.
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.
Progression-free survival (PFS)
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
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)
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.
Click on the lead sponsor to view all of their trials.
Global Coalition for Adaptive Research
Lead sponsor
Bayer
Collaborator
Kazia Therapeutics Limited
Collaborator
Kintara Therapeutics, Inc.
Collaborator
Biohaven Pharmaceuticals, Inc.
Collaborator
Vigeo Therapeutics, Inc.
Collaborator
Polaris Group
Collaborator
AstraZeneca
Collaborator
Knoa Pharma
Collaborator
