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

Glioblastoma Clinical Trial

— GBM AGILE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03970447
• Other study ID #: GCAR-7213
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 30, 2019
• Est. completion date: June 2028

Study information

• Verified date: June 2024
• Source: Global Coalition for Adaptive Research
• Contact: Patient Information
• Phone: 310-598-3199
• Email: patientinfo[@]gcaresearch.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1030
• Est. completion date: June 2028
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 > 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. 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 > 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. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• 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:
• 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
• 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.

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

Locations

Country	Name	City	State
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Northern Sydney Cancer Centre/Royal North Shore Hospital	St Leonards	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Canada	Montreal Neurological Institute and Hospital, McGill University	Montréal	Quebec
Canada	Université de Sherbrooke	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
France	Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer	Bron
France	Hopital de la Timone	Marseille
France	Hopital Piti-Salpetriere	Paris
Germany	Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie	Cologne
Germany	Dr. Senckenbergisches Institut für Neuroonkologie	Frankfurt
Germany	Universitätsklinik Heidelberg	Heidelberg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsklinikum Tübingen	Tübingen
Switzerland	Universitätsspital Basel	Basel
Switzerland	Centre Hospitalier Universitaire Vaudois Lausanne	Lausanne	Vaud
Switzerland	University Hospital Zurich	Zürich
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Texas Oncology - Austin	Austin	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina - Hollings Cancer Center	Charleston	South Carolina
United States	University of Virginia Health	Charlottesville	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Ohio State University Cancer Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	University of California, San Diego	La Jolla	California
United States	Cedars Sinai - Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Froedtert Hospital/Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Yale Cancer Center / Smilow Cancer Hospital	New Haven	Connecticut
United States	LSU Health Sciences Center - New Orleans	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Perlmutter Cancer Center, NYU Langone Health	New York	New York
United States	St. Joseph Hospital	Orange	California
United States	University of Pennsylvania - Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center - Rochester	Rochester	Minnesota
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	Comprehensive Cancer Center of Wake Forest	Winston-Salem	North Carolina

Sponsors (7)

Lead Sponsor	Collaborator
Global Coalition for Adaptive Research	Bayer, Biohaven Pharmaceuticals, Inc., Kazia Therapeutics Limited, Kintara Therapeutics, Inc., Polaris Group, Vigeo Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.
Secondary	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.	From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Secondary	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.	From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.
Secondary	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.	From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

External Links

•   Global Coalition for Adaptive Research Website