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 (\*).

Interventions

• Temozolomide · DRUG

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

• Lomustine · DRUG

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

• Regorafenib · DRUG

  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

• Paxalisib · DRUG

  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 · DRUG

  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 · DRUG

  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 · DRUG

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

• ADI-PEG 20 · BIOLOGICAL

  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 · DRUG

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

• Tinostamustine · DRUG

  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.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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.

Sites (63)

• 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
• University of Washington Medical Center, Seattle, Washington · ACTIVE_NOT_RECRUITING
• Froedtert Hospital/Medical College of Wisconsin, Milwaukee, Wisconsin · ACTIVE_NOT_RECRUITING
• Northern Sydney Cancer Centre/Royal North Shore Hospital, St Leonards, New South Wales, Australia · RECRUITING
• Calvary Mater Newcastle, Waratah, New South Wales, Australia · RECRUITING
• Royal Brisbane and Women's Hospital, Herston, Queensland, Australia · RECRUITING
• Flinders Medical Centre, Bedford Park, South Australia, Australia · RECRUITING
• Austin Health, Heidelberg, Victoria, Australia · RECRUITING
• Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia · RECRUITING
• Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada · RECRUITING
• Princess Margaret Cancer Centre, Toronto, Ontario, Canada · RECRUITING
• Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada · RECRUITING
• Université de Sherbrooke, Sherbrooke, Quebec, Canada · ACTIVE_NOT_RECRUITING
• Centre Hospitalier Lyon Sud / Hôpital Neurologique P. Wertheimer, Bron, France · RECRUITING
• Hopital de la Timone, Marseille, France · RECRUITING
• Hopital Piti-Salpetriere, Paris, France · RECRUITING
• Uniklinik Koeln - Zentrum fuer Neurologie und Psychiatrie, Cologne, Germany · ACTIVE_NOT_RECRUITING
• Dr. Senckenbergisches Institut für Neuroonkologie, Frankfurt, Germany · RECRUITING
• Universitätsklinik Heidelberg, Heidelberg, Germany · RECRUITING
• Universitaetsklinikum Heidelberg - Neurologische Klinik, Mannheim, Germany · RECRUITING
• Universitätsklinikum Regensburg, Regensburg, Germany · RECRUITING
• Universitätsklinikum Tübingen, Tübingen, Germany · RECRUITING
• Centre Hospitalier Universitaire Vaudois Lausanne, Lausanne, Canton of Vaud, Switzerland · RECRUITING
• University Hospital Zurich, Zurich, Switzerland · RECRUITING