NCT03970447

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

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

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 2,250 (estimated)
• Sponsor: Global Coalition for Adaptive Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Glioblastoma

Interventions

Type	Name	Description
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
DRUG	AZD1390	Standard Regimen Newly Diagnosed: Given once daily on days of radiation and once daily for 14 consecutive days after completion of radiation.
DRUG	Tinostamustine	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.

Timeline

• Start date: 2019-07-30
• Primary completion: 2028-06-01
• Completion: 2030-06-01
• First posted: 2019-05-31
• Last updated: 2026-04-08

Locations

63 sites across 6 countries: United States, Australia, Canada, France, Germany, Switzerland

Regulatory

• FDA-regulated drug study