Clinical trial NCT04164901: Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Grade 2 Glioma
Residual Glioma
Recurrent Glioma
Keywords: AG-881
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2019-11-15
Enrollment: 331
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants randomized in a 1:1 allocation (vorasidenib vs Placebo)
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 30 months
Secondary outcomes:
measure: Time to Next Intervention (TTNI)
timeFrame: Up to approximately 3 years
measure: Tumor Growth Rate (TGR)
timeFrame: every 6 months, up to 2 years and 9 months
measure: Objective Response (OR) as Assessed by the Blinded Independent Review Committee (BIRC)
timeFrame: approximatively 30 months
measure: Complete Response (CR) and Partial Response (PR) by BIRC
timeFrame: Approximatively 30 months
measure: Time to Response (TTR) by BIRC
timeFrame: Approximatively 30 months
measure: Time to CR+PR by BIRC
timeFrame: Approximatively 30 months
measure: Duration of Response (DoR)
timeFrame: Approximatively 30 months
measure: Duration of CR+PR
timeFrame: Approximatively 30 months
measure: Overall Survival (OS)
timeFrame: Approximatively 30 months
measure: Progression-Free Survival (PFS) by the Investigator
timeFrame: Approximatively 30 months
measure: Health-Related Quality of Life (FACT-Br)
timeFrame: Approximatively 30 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: UCLA Oncology Center
state: California
city: Orange
country: United States
facility: University of California Irvine - Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: New Haven
country: United States
facility: Yale University, Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center - University of Miami Hospital and Clinics
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Scarborough
country: United States
facility: Maine Medical Partners Neurology
state: Maine
city: Baltimore
country: United States
facility: John Hopkins Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Metro Minnesota Community Oncology
state: Minnesota
city: Rochester
country: United States
facility: Mayo Comprehensive Cancer
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: The University of Utah, Huntsman Cancer Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Lyon
country: France
facility: Hôpital Pierre Wertheimer
city: Marseille
country: France
facility: Hopitaux de La Timone
city: Paris
country: France
facility: Hospitalier Pitié Salpétrière
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Mannheim
country: Germany
facility: Klinikum Mannheim Universitätsklinikum
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
state: Piemonte
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Padua
country: Italy
facility: Istituto Oncologico Veneto - I.R.C.C.S.
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Minami-Ku
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Bunkyō-Ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Leidschendam
country: Netherlands
facility: Haaglanden MC, Antoniushove
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaire de Genève
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: England
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Edinburgh
country: United Kingdom
facility: Western General Hospital Edinburgh - PPDS
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
References:
citation: 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.