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

Recurrent Glioma Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04164901
• Other study ID #: AG881-C-004
• Secondary ID: 2019-002481-13
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 5, 2020
• Est. completion date: August 2027

Study information

• Verified date: December 2023
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 331
• Est. completion date: August 2027
• Est. primary completion date: September 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key 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 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).

Related Conditions & MeSH terms

• Glioma
• Grade 2 Glioma
• Recurrence
• Recurrent Glioma
• Residual Glioma

Intervention

Drug:
• Vorasidenib
Vorasidenib oral film-coated tablets
• Matching Placebo
Matching Placebo oral tablets

Locations

Country	Name	City	State
Canada	London Health Sciences Centre	London	Ontario
Canada	McGill University Health Center	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BC Cancer Agency	Vancouver	British Columbia
France	Centre Hospitalier Universitaire de Lille	Lille
France	Hôpital Pierre Wertheimer	Lyon
France	Hopitaux de La Timone	Marseille
France	Hospitalier Pitié Salpétrière	Paris
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Klinikum Mannheim Universitätsklinikum	Mannheim
Israel	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
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	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino	Piemonte
Japan	The University of Tokyo Hospital	Bunkyo-Ku	Tokyo
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kyoto University Hospital	Kyoto
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto
Japan	Hiroshima University Hospital	Minami-Ku	Hiroshima
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Okayama University Hospital	Okayama
Japan	Fujita Health University Hospital	Toyoake	Aichi
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Haaglanden MC, Antoniushove	Leidschendam	Zuid-Holland
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Spain	Hospital Universitario Vall d'Hebrón	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Switzerland	Hôpitaux Universitaire de Genève	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Universitätsspital Zürich	Zürich
United Kingdom	Western General Hospital Edinburgh - PPDS	Edinburgh
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Freeman Hospital	Newcastle Upon Tyne	England
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	John Hopkins Cancer Center	Baltimore	Maryland
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	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego	La Jolla	California
United States	University of Kentucky	Lexington	Kentucky
United States	UCLA Oncology Center	Los Angeles	California
United States	Sylvester Comprehensive Cancer Center - University of Miami Hospital and Clinics	Miami	Florida
United States	Metro Minnesota Community Oncology	Minneapolis	Minnesota
United States	Tennessee Oncology	Nashville	Tennessee
United States	Yale University, Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California Irvine - Hospital	Orange	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Comprehensive Cancer	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	The University of Utah, Huntsman Cancer Hospital	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Maine Medical Partners Neurology	Scarborough	Maine
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	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.	Up to approximately 30 months
Secondary	Time to Next Intervention		Up to approximately 3 years