Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)

Phase 3

Active, not recruiting

• Conditions: Grade 2 Glioma; Residual Glioma; Recurrent Glioma
• Interventions: Drug: Vorasidenib; 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

Study Timeline

• Study First Submitted: 2019-11-11
• Study First Submitted QC: 2019-11-14
• Study First Posted: 2019-11-15
• Study Start: 2020-01-05
• Primary Completion: 2022-09-06
• Results First Submitted: 2023-09-05
• Results First Submitted QC: 2023-11-01
• Results First Posted: 2023-11-24
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-01
• Last Update Posted: 2023-12-05
• Study Completion: 2027-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 331

Inclusion Criteria

• 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

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Exclusion Criteria

• 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).

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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	Up to approximately 3 years

Trial Locations

Locations (84)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

The Royal Marsden NHS Foundation Trust; 🇬🇧 Sutton, Surrey, United Kingdom

Sylvester Comprehensive Cancer Center - University of Miami Hospital and Clinics; 🇺🇸 Miami, Florida, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

City of Hope; 🇺🇸 Duarte, California, United States

Maine Medical Partners Neurology; 🇺🇸 Scarborough, Maine, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Indiana University Medical Center; 🇺🇸 Indianapolis, Indiana, United States

Ospedale Bellaria; 🇮🇹 Bologna, Italy

Columbia University Medical Center; 🇺🇸 New York, New York, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Universitätsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Centre Hospitalier Universitaire de Lille; 🇫🇷 Lille, France

Hospitalier Pitié Salpétrière; 🇫🇷 Paris, France

Hôpital Pierre Wertheimer; 🇫🇷 Lyon, France

Universitätsspital Zürich; 🇨🇭 Zürich, Switzerland

Freeman Hospital; 🇬🇧 Newcastle Upon Tyne, England, United Kingdom

Metro Minnesota Community Oncology; 🇺🇸 Minneapolis, Minnesota, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

University Hospital, Kyoto Prefectural University of Medicine; 🇯🇵 Kyoto, Japan

UCLA Oncology Center; 🇺🇸 Los Angeles, California, United States

John Hopkins Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Yale University, Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

BC Cancer Agency; 🇨🇦 Vancouver, British Columbia, Canada

McGill University Health Center; 🇨🇦 Montreal, Quebec, Canada

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Chaim Sheba Medical Center; 🇮🇱 Ramat-Gan, Israel

Azienda Ospedaliera Città della Salute e della Scienza di Torino; 🇮🇹 Torino, Piemonte, Italy

Istituto Nazionale Tumori Regina Elena; 🇮🇹 Roma, Italy

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Italy

Istituto Oncologico Veneto - I.R.C.C.S.; 🇮🇹 Padua, Italy

Nagoya University Hospital; 🇯🇵 Nagoya, 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

Haaglanden MC, Antoniushove; 🇳🇱 Leidschendam, Zuid-Holland, Netherlands

Okayama University Hospital; 🇯🇵 Okayama, Japan

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

Kyoto University Hospital; 🇯🇵 Kyoto, Japan

Hospital Universitario Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland

Hôpitaux Universitaire de Genève; 🇨🇭 Geneva, Switzerland

Western General Hospital Edinburgh - PPDS; 🇬🇧 Edinburgh, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

University of California Irvine - Hospital; 🇺🇸 Orange, California, United States

University of California San Diego; 🇺🇸 La Jolla, California, United States

Mayo Clinic Jacksonville; 🇺🇸 Jacksonville, Florida, United States

University of Colorado Hospital - Anschutz Cancer Pavilion; 🇺🇸 Aurora, Colorado, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

The University of Utah, Huntsman Cancer Hospital; 🇺🇸 Salt Lake City, Utah, United States

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Fujita Health University Hospital; 🇯🇵 Toyoake, Aichi, Japan

Mayo Comprehensive Cancer; 🇺🇸 Rochester, Minnesota, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

University of Pittsburgh Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Hopitaux de La Timone; 🇫🇷 Marseille, France

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Kumamoto University Hospital; 🇯🇵 Kumamoto, Japan

Klinikum Mannheim Universitätsklinikum; 🇩🇪 Mannheim, Germany

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States