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NCT Number: NCT04164901

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Grade 2 Glioma Glioma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Recurrent Glioma Residual Glioma

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

BC Cancer Agency, Vancouver, British Columbia, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Vorasidenib

Drug

Vorasidenib oral film-coated tablets

Other names: AG-881

Matching Placebo

Drug

Matching Placebo oral tablets

Primary outcomes

  1. Progression-Free Survival (PFS)

    Time frame: 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 outcomes

  1. Time to Next Intervention (TTNI)

    Time frame: 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.

  2. Tumor Growth Rate (TGR)

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

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

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

    Time frame: 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).

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

    Time frame: Approximatively 30 months

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

  5. Time to Response (TTR) by BIRC

    Time frame: 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

  6. Time to CR+PR by BIRC

    Time frame: 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)

  7. Duration of Response (DoR)

    Time frame: 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

  8. Duration of CR+PR

    Time frame: 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

  9. Overall Survival (OS)

    Time frame: 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.

  10. Progression-Free Survival (PFS) by the Investigator

    Time frame: Approximatively 30 months

    PFS as assessed by the Investigator per the modified RANO-LGG

  11. Health-Related Quality of Life (FACT-Br)

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Institut de Recherches Internationales Servier

Other

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2022
Study completion
2028
First posted
Nov 15, 2019
Registry last updated
Apr 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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