Vorasidenib for Glioma

Not currently recruiting at 95 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.

Must not be taking: IDH inhibitors

Disqualifiers: Prior anticancer therapy, High-risk features

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, vorasidenib, for individuals with Grade 2 glioma, a type of brain tumor. Researchers aim to determine if vorasidenib benefits patients with a specific genetic change (IDH1 or IDH2 mutation) after surgery but before any other cancer treatment. Participants will receive either vorasidenib or a placebo to compare outcomes. Those who have undergone surgery for glioma and possess an IDH mutation may be suitable candidates for this study. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that vorasidenib is likely to be safe for humans?

Research has shown that vorasidenib, a treatment under study for certain brain tumors, is generally safe. In earlier studies, patients with non-enhancing glioma tolerated vorasidenib well. The safety data from these studies suggest that any side effects were manageable and not too severe.

Furthermore, new findings from the INDIGO study confirmed that vorasidenib effectively treats tumors and maintains a manageable safety profile. This indicates that while the treatment works well, it does not cause major safety concerns for most patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioma?

Vorasidenib is unique because it specifically targets the IDH1 and IDH2 mutations common in glioma, which sets it apart from the typical chemotherapy and radiation treatments usually used for this condition. Most treatments for glioma focus on destroying rapidly dividing cells, but Vorasidenib works by inhibiting mutant enzymes that contribute to tumor growth. Researchers are excited about Vorasidenib because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes for patients with these specific genetic mutations.

What evidence suggests that vorasidenib might be an effective treatment for glioma?

Research has shown that vorasidenib, which participants in this trial may receive, can lower tumor 2-HG levels by over 90% in certain brain tumors with IDH mutations. In studies, vorasidenib consistently outperformed a placebo for patients with IDH1/2-mutated diffuse glioma. This treatment significantly extended the time patients lived without their cancer worsening. These findings suggest that vorasidenib could be a promising option for treating certain types of glioma. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11628568/

Vorasidenib: First Approval - PMC - PubMed Central Relative to combined data from untreated control tumors, tumor 2-HG concentrations were reduced by 92.6% (95% credible interval 76.1–97.6) in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7025383/

Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual ... Vorasidenib was recently reported to reduce 2-HG levels by >90% in mIDH gliomas in humans, as demonstrated by analysis of postdrug treatment tumor samples ...

3. onclive.com onclive.com/view/vorasidenib-shows-consistent-efficacy-with-manageable-safety-in-idh1-2-mutant-diffuse-glioma

Vorasidenib Shows Consistent Efficacy With Manageable ... Updated INDIGO data reveal that vorasidenib continues to showcase improved efficacy over placebo in patients with IDH1/2-mutated diffuse glioma.

4. researchgate.net researchgate.net/publication/384731374_Vorasidenib_First_Approval

(PDF) Vorasidenib: First Approval Approval was based on results from the multinational phase III INDIGO trial, in which vorasidenib significantly improved progression-free ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/01/NCT04164901/Prot_000.pdf

CLINICAL STUDY PROTOCOL AG881-C-004 suppression by vorasidenib. Based on the observed safety and efficacy data in subjects with glioma, vorasidenib may serve as a novel molecularly targeted ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT293385

Vorasidenib (VOR; AG-881), an inhibitor of mutant IDH1 ... Conclusions: In this previously treated population with non-enhancing glioma, VOR was associated with a favorable safety profile. The study results also ...

7. synapse.patsnap.com synapse.patsnap.com/drug/2e53957b0d6943faaf96ff666e51031b

Vorasidenib - Drug Targets, Indications, Patents PURPOSE: The role of IDH inhibitors in recurrent high-grade gliomas (HGG) is not well described. We present the outcomes of patients with HGG that were treated ...