Vorasidenib for Glioma

Recruiting at 90 trial locations

Overseen By Institut de Recherches Internationales Servier Clinical Studies Department

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Agios Pharmaceuticals, Inc.

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 30 months

331 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing an oral medication called vorasidenib in patients with a specific type of brain tumor that has a genetic mutation. The drug aims to block proteins that help the tumor grow, potentially slowing or stopping its growth.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial excludes participants who have had prior anticancer therapy other than surgery, it's possible that some medications might need to be paused. Please consult with the trial team for specific guidance.

Is Vorasidenib safe for humans?

Vorasidenib has been tested in humans and was generally well tolerated in clinical trials for glioma, with ongoing follow-up to monitor safety. ^{1 2 3 4 5}

What makes the drug Vorasidenib unique for treating glioma?

Vorasidenib is unique because it is a first-in-class drug that can penetrate the brain and specifically targets and inhibits mutant forms of the IDH1 and IDH2 enzymes, which are commonly mutated in lower grade gliomas. This targeted approach helps reduce the production of a harmful substance called D-2-hydroxyglutarate in the tumor, potentially slowing tumor growth and progression. ^{1 2 4 5 6}

Eligibility Criteria

This trial is for people at least 12 years old with a Grade 2 glioma brain tumor that has returned or remains after surgery. They must weigh over 40 kg, have had no other cancer treatments like chemo or radiation, and not need immediate therapy. Participants require confirmed IDH1/IDH2 mutations and measurable disease on MRI.

Inclusion Criteria

I had surgery for glioma between 1 and 5 years ago and haven't had any other cancer treatments.

My MRI shows measurable disease that doesn't enhance with contrast.

I am mostly active and can carry out my daily activities without help.

Exclusion Criteria

I have only had surgery for my glioma, no other cancer treatments.

My brain tumor is considered high-risk, possibly affecting my brainstem or causing significant symptoms or uncontrolled seizures despite treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive orally administered vorasidenib 40 mg or placebo daily

Up to approximately 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

Treatment Details

Interventions

• Matching Placebo
• Vorasidenib

Trial Overview The INDIGO study tests Vorasidenib against a placebo in patients with specific recurrent brain tumors. About 340 participants will be randomly assigned to take either the drug or placebo orally once daily, without knowing which one they're receiving.

Participant Groups

Group I: Vorasidenib Experimental Treatment 1 Intervention

Vorasidenib 40 mg, continuous daily dosing.

Group II: Matching Placebo Placebo Group 1 Intervention

Matching placebo 40 mg, continuous daily dosing.

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials

55

Recruited

4,200+

Institut de Recherches Internationales Servier

Lead Sponsor

Trials

91

Recruited

67,100+

Findings from Research

The maximum-tolerated dose (MTD) of cediranib in children with recurrent CNS tumors was initially set at 32 mg/m²/day, but excessive toxicities led to concerns about its long-term tolerability.

At a lower dose of 20 mg/m²/day, cediranib still showed poor tolerability, indicating that both doses may not be suitable for extended treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. Kieran, MW., Chi, S., Goldman, S., et al.[2018]

In a phase II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

Vandetanib, administered at a maximum tolerated dose of 145 mg/m² per day, showed a manageable safety profile in children with diffuse intrinsic pontine glioma, with only one patient experiencing a dose-limiting toxicity of grade 3 diarrhea.

The study found that higher baseline levels of vascular endothelial growth factor (VEGF) were associated with longer progression-free survival, while increases in VEGF during treatment correlated with shorter progression-free survival, indicating the importance of monitoring VEGF levels during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. Broniscer, A., Baker, JN., Tagen, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Phase I/II trial of vorinostat combined with temozolomide and radiation therapy for newly diagnosed glioblastoma: results of Alliance N0874/ABTC 02. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. [2018]

4. England pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. [2022]