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

Phase 3Active Not RecruitingNCT04164901

Institut de Recherches Internationales Servier331 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

331

Conditions

Grade 2 Glioma Residual Glioma Recurrent Glioma

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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).

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

Outcomes

Primary Outcomes

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.

Time frame: Up to approximately 30 months

Secondary Outcomes

Time to Next Intervention (TTNI)

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.

Time frame: Up to approximately 3 years

Tumor Growth Rate (TGR)

Calculated as the mean of the percentage change in tumor volume every 6 months

Time frame: every 6 months, up to 2 years and 9 months

Objective Response (OR) as Assessed by the Blinded Independent Review Committee (BIRC)

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).

Time frame: approximatively 30 months

Complete Response (CR) and Partial Response (PR) by BIRC

CR and PR is defined as a BOR of CR or PR as assessed by BIRC per the modified RANO-LGG