Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
- Conditions
- Grade 2 GliomaResidual GliomaRecurrent Glioma
- Interventions
- Drug: Matching Placebo
- Registration Number
- NCT04164901
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 340 participants are planned to be randomized 1:1 to receive orally administered vorasidenib 40 mg QD or placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 331
- Be at least 12 years of age and weigh at least 40 kg.
- Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.
- Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total resection), with the most recent surgery having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before the date of randomization, and no other prior anticancer therapy, including chemotherapy and radiotherapy and not be in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
- Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by central laboratory testing during the Prescreening period and available 1p19q status by local testing (eg, fluorescence in situ hybridization [FISH], comparative genomic hybridization [CGH] array, sequencing) using an accredited laboratory.
- Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC.
- Have a Karnofsky Performance Scale (KPS) score (for participants ≥16 years of age) or Lansky Play Performance Scale (LPPS) score (for participants <16 years of age) of ≥80%.
Key
- Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including systemic chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser ablation, etc.
- Have features assessed as high-risk by the Investigator, including brainstem involvement either as primary location or by tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor in the opinion of the Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with activities of daily life AND failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vorasidenib Vorasidenib Vorasidenib 40 mg, continuous daily dosing. Matching Placebo Matching Placebo Matching placebo 40 mg, continuous daily dosing.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to approximately 30 months PFS is defined as the time from date of randomization to date of first documented radiographic PD (as assessed by the blinded independent review committee (BIRC) per modified Response Assessment for Neuro-oncology for Low-Grade Gliomas or date of death due to any cause, whichever occurs earlier.
- Secondary Outcome Measures
Name Time Method Time to Next Intervention (TTNI) Up to approximately 3 years TTNI is defined as the time from randomization to the initiation of the first subsequent anticancer therapy (including vorasidenib, for subjects randomized to placebo who subsequently cross over) or death due to any cause.
Tumor Growth Rate (TGR) every 6 months, up to 2 years and 9 months Calculated as the mean of the percentage change in tumor volume every 6 months
Objective Response (OR) as Assessed by the Blinded Independent Review Committee (BIRC) approximatively 30 months OR is defined as a best overall response (BOR) of Complete Response, Partial Rresponse, or minor Response as assessed by the BIRC per the modified Response Assessment in Neuro-oncology for Low-grade Gliomas (RANO-LGG).
Complete Response (CR) and Partial Response (PR) by BIRC Approximatively 30 months CR and PR is defined as a BOR of CR or PR as assessed by BIRC per the modified RANO-LGG
Time to Response (TTR) by BIRC Approximatively 30 months TTR is defined as the time from the date of randomization to the date of first documented CR, PR, or mR by BIRC per the modified RANO-LGG
Time to CR+PR by BIRC Approximatively 30 months Time to CR+PR is defined as defined as the time from the date of randomization to the date of first documented CR or PR for subjects with CR or PR per the modified RANO-LGG (by BIRC)
Duration of Response (DoR) Approximatively 30 months DoR is defined as the time from the date of first documented CR, PR, or mR to the date of death due to any cause or date of first documented radiographic Prgressive Disease, whichever occurred earlier
Duration of CR+PR Approximatively 30 months Duration of CR+PR is defined as the time from the date of first documented CR or PR to the date of death due to any cause or first documented radiographic PD, whichever occurred earlier
Overall Survival (OS) Approximatively 30 months OS wad defined as the time from the date of randomization to the date of death due to any cause or data cutoff.
Progression-Free Survival (PFS) by the Investigator Approximatively 30 months PFS as assessed by the Investigator per the modified RANO-LGG
Health-Related Quality of Life (FACT-Br) Approximatively 30 months Health-Related Quality of Life (HRQoL) Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a 50-item measure comprising the following subscales: Physical Well-Being, Functional Well-Being, Emotional Well-Being, and Social Well-Being subscales from the FACT-General (FACT-G), with the addition of a 23-item brain tumor-specific subscale. These subscales are summed to provide a total score. The total score is given at the end of treatment and total scores range from 0 to 200. Higher scores indicate a better HRQoL
Trial Locations
- Locations (84)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
City of Hope
🇺🇸Duarte, California, United States
University of California San Diego
🇺🇸La Jolla, California, United States
UCLA Oncology Center
🇺🇸Los Angeles, California, United States
University of California Irvine - Hospital
🇺🇸Orange, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Yale University, Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Sylvester Comprehensive Cancer Center - University of Miami Hospital and Clinics
🇺🇸Miami, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Maine Medical Partners Neurology
🇺🇸Scarborough, Maine, United States
John Hopkins Cancer Center
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Metro Minnesota Community Oncology
🇺🇸Minneapolis, Minnesota, United States
Mayo Comprehensive Cancer
🇺🇸Rochester, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The University of Utah, Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
BC Cancer Agency
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Lille
🇫🇷Lille, France
Hôpital Pierre Wertheimer
🇫🇷Lyon, France
Hopitaux de La Timone
🇫🇷Marseille, France
Hospitalier Pitié Salpétrière
🇫🇷Paris, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Klinikum Mannheim Universitätsklinikum
🇩🇪Mannheim, Germany
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Ospedale Bellaria
🇮🇹Bologna, Italy
Istituto Oncologico Veneto - I.R.C.C.S.
🇮🇹Padua, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Aichi, Japan
Hiroshima University Hospital
🇯🇵Minami-Ku, Hiroshima, Japan
The University of Tokyo Hospital
🇯🇵Bunkyō-Ku, Tokyo, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
University Hospital, Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Haaglanden MC, Antoniushove
🇳🇱Leidschendam, Zuid-Holland, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Hospital Universitario Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hôpitaux Universitaire de Genève
🇨🇭Geneva, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Universitätsspital Zürich
🇨🇭Zürich, Switzerland
Freeman Hospital
🇬🇧Newcastle Upon Tyne, England, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, Surrey, United Kingdom
Western General Hospital Edinburgh - PPDS
🇬🇧Edinburgh, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom