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

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

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).

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
Progression-Free Survival (PFS) by the Investigator	Approximatively 30 months	PFS as assessed by the Investigator per the modified RANO-LGG
Time to Next Intervention (TTNI)	Up to approximately 3 years	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.
Tumor Growth Rate (TGR)	every 6 months, up to 2 years and 9 months	Calculated as the mean of the percentage change in tumor volume every 6 months
Objective Response (OR) as Assessed by the Blinded Independent Review Committee (BIRC)	approximatively 30 months	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).
Complete Response (CR) and Partial Response (PR) by BIRC	Approximatively 30 months	CR and PR is defined as a BOR of CR or PR as assessed by BIRC per the modified RANO-LGG
Time to Response (TTR) by BIRC	Approximatively 30 months	TTR is defined as the time from the date of randomization to the date of first documented CR, PR, or mR by BIRC per the modified RANO-LGG
Time to CR+PR by BIRC	Approximatively 30 months	Time to CR+PR is defined as defined as the time from the date of randomization to the date of first documented CR or PR for subjects with CR or PR per the modified RANO-LGG (by BIRC)
Duration of Response (DoR)	Approximatively 30 months	DoR is defined as the time from the date of first documented CR, PR, or mR to the date of death due to any cause or date of first documented radiographic Prgressive Disease, whichever occurred earlier
Duration of CR+PR	Approximatively 30 months	Duration of CR+PR is defined as the time from the date of first documented CR or PR to the date of death due to any cause or first documented radiographic PD, whichever occurred earlier
Overall Survival (OS)	Approximatively 30 months	OS wad defined as the time from the date of randomization to the date of death due to any cause or data cutoff.
Health-Related Quality of Life (FACT-Br)	Approximatively 30 months	Health-Related Quality of Life (HRQoL) Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a 50-item measure comprising the following subscales: Physical Well-Being, Functional Well-Being, Emotional Well-Being, and Social Well-Being subscales from the FACT-General (FACT-G), with the addition of a 23-item brain tumor-specific subscale. These subscales are summed to provide a total score. The total score is given at the end of treatment and total scores range from 0 to 200. Higher scores indicate a better HRQoL

Trial Locations

Locations (84): University of Alabama at Birmingham
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Birmingham, Alabama, United States
City of Hope
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Duarte, California, United States
University of California San Diego
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La Jolla, California, United States
UCLA Oncology Center
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Los Angeles, California, United States
University of California Irvine - Hospital
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Orange, California, United States
University of California San Francisco
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San Francisco, California, United States
Stanford Cancer Center
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Stanford, California, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
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Aurora, Colorado, United States
Yale University, Yale Cancer Center
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New Haven, Connecticut, United States
Mayo Clinic Jacksonville
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Jacksonville, Florida, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States