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

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.

All institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (\*).

Conditions

• Glioblastoma

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

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.

Sponsors & Collaborators

• Bayer

  collaborator INDUSTRY

• Kazia Therapeutics Limited

  collaborator INDUSTRY

• Kintara Therapeutics, Inc.

  collaborator INDUSTRY

• Biohaven Pharmaceuticals, Inc.

  collaborator INDUSTRY

• Vigeo Therapeutics, Inc.

  collaborator INDUSTRY

• Polaris Group

  collaborator INDUSTRY

• AstraZeneca

  collaborator INDUSTRY

• Knoa Pharma

  collaborator UNKNOWN

• Global Coalition for Adaptive Research

  lead OTHER

Principal Investigators

• Tim Cloughesy, MD · GCAR CMO and GBM AGILE Global PI

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-07-30

Primary Completion

2028-06-30

Completion

2030-06-30

FDA Drug

Yes

Countries

• United States
• Australia
• Canada
• France
• Germany
• Switzerland

Study Locations