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

NCT ID: NCT04164901

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 331 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-05
• Study Completion Date: 2028-05-31

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.

Conditions

Grade 2 Glioma; Residual Glioma; Recurrent Glioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vorasidenib

Vorasidenib 40 mg, continuous daily dosing.

Group Type: EXPERIMENTAL

Vorasidenib

Intervention Type: DRUG

Vorasidenib oral film-coated tablets

Matching Placebo

Matching placebo 40 mg, continuous daily dosing.

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

Matching Placebo oral tablets

Interventions

Vorasidenib

Vorasidenib oral film-coated tablets

Intervention Type: DRUG

Matching Placebo

Matching Placebo oral tablets

Intervention Type: DRUG

Other Intervention Names

AG-881

Eligibility Criteria

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%.

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).

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

St 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

Turin, Piedmont, 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-ken, Japan

Fujita Health University Hospital

Toyoake, Aichi-ken, 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, South 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

Zurich, , 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

Countries

United States; Canada; France; Germany; Israel; Italy; Japan; Netherlands; Spain; Switzerland; United Kingdom

References

Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry JR, Giglio P, de la Fuente M, Maher EA, Schoenfeld S, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Cloughesy TF; INDIGO Trial Investigators. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med. 2023 Aug 17;389(7):589-601. doi: 10.1056/NEJMoa2304194. Epub 2023 Jun 4.

Reference Type: RESULT

PMID: 37272516 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Study Documents

Document Type: Individual Participant Data Set

View Document

Other Identifiers

2019-002481-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-512961-15-00

Identifier Type: CTIS

Identifier Source: secondary_id

AG881-C-004

Identifier Type: -

Identifier Source: org_study_id