A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (NCT03970447) — Australia Trial Details

Condition(s) studied

Glioblastoma

Investigational drug(s) / intervention(s)

Temozolomide →Lomustine →Regorafenib →RadiationPaxalisib →VAL-083VT1021Troriluzole →ADI-PEG 20 →AZD1390 →Tinostamustine

Temozolomide: Dosage Form: Capsule for oral administration Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, or 250 mg

Lomustine: Dosage Form: Capsule for oral administration Strength: 5 mg, 10 mg, 40 mg, and 100 mg

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: 60 Gy

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

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.

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.

Troriluzole: Dosage Form: Capsule for oral administration Strength: 100 mg Standard Regimen: Dose as confirmed through the dose finding phase orally BID.

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

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

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.

Study 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 (\*).

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

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 \> 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. 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 \> 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.

Primary outcome measure(s)

Overall Survival (OS) — 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.

Trial sites (63)

Facility	City	Region	Status
University of Alabama at Birmingham	Birmingham	Alabama	Recruiting
University of California, San Diego	La Jolla	California	Recruiting
Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California	Recruiting
University of California, Los Angeles	Los Angeles	California	Active Not Recruiting
St. Joseph Hospital	Orange	California	Recruiting
University of California, San Francisco	San Francisco	California	Active Not Recruiting
Stanford Cancer Center	Stanford	California	Completed
University of Colorado Denver	Aurora	Colorado	Recruiting
Yale Cancer Center / Smilow Cancer Hospital*	New Haven	Connecticut	Recruiting
Mayo Clinic Cancer Center	Jacksonville	Florida	Completed
Sylvester Comprehensive Cancer Center*	Miami	Florida	Recruiting
Moffitt Cancer Center	Tampa	Florida	Active Not Recruiting
Piedmont Atlanta Hospital	Atlanta	Georgia	Active Not Recruiting
Winship Cancer Institute of Emory University	Atlanta	Georgia	Completed
LSU Health Sciences Center - New Orleans	New Orleans	Louisiana	Completed
Massachusetts General Hospital	Boston	Massachusetts	Recruiting
Dana Farber Cancer Institute	Boston	Massachusetts	Recruiting
Henry Ford Health System	Detroit	Michigan	Completed
Allina Health Systems/Abbott Northwestern Hospital	Minneapolis	Minnesota	Recruiting
Mayo Clinic Cancer Center - Rochester	Rochester	Minnesota	Completed
University of Mississippi Medical Center	Jackson	Mississippi	Completed
Washington University School of Medicine - Siteman Cancer Center	St Louis	Missouri	Completed
Perlmutter Cancer Center, NYU Langone Health	New York	New York	Active Not Recruiting
Icahn School of Medicine at Mount Sinai	New York	New York	Recruiting
Columbia University Medical Center	New York	New York	Recruiting
Memorial Sloan Kettering Cancer Center*	New York	New York	Recruiting
Duke University Medical Center	Durham	North Carolina	Active Not Recruiting
Comprehensive Cancer Center of Wake Forest*	Winston-Salem	North Carolina	Recruiting
University Hospitals Cleveland Medical Center*	Cleveland	Ohio	Recruiting
Cleveland Clinic	Cleveland	Ohio	Recruiting
Ohio State University Cancer Center	Columbus	Ohio	Active Not Recruiting
University of Pennsylvania - Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania	Active Not Recruiting
Allegheny General Hospital	Pittsburgh	Pennsylvania	Completed
University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania	Recruiting
Medical University of South Carolina - Hollings Cancer Center	Charleston	South Carolina	Recruiting
Texas Oncology - Austin	Austin	Texas	Active Not Recruiting
University of Texas Southwestern Medical Center	Dallas	Texas	Active Not Recruiting
University of Texas - MD Anderson Cancer Center	Houston	Texas	Recruiting
University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah	Recruiting
University of Virginia Health	Charlottesville	Virginia	Recruiting

+ 23 more sites — see the full list on the official registry below.

On this site

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