Testing Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer

NCT07215910 | Not Yet Recruiting Phase 3

• 1 other identifier: A072301
• Study Type: interventional
• Target: 408
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase III trial compares the effect of vorasidenib to placebo in combination with usual treatment, temozolomide, in treating patients with newly diagnosed grade 3 astrocytoma after radiation. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. Vorasidenib citrate blocks the proteins made by the mutated IDH1 and IDH2 genes, which may help keep tumor cells from growing. It is a type of enzyme inhibitor and a type of targeted therapy. Adding vorasidenib to the usual treatment, temozolomide, may be more effective than temozolomide alone in treating patients with newly diagnosed grade 3 astrocytoma after radiation therapy.

Conditions

Astrocytoma, IDH-Mutant, Grade 3

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) by blinded independent central review (BICR)

  This is defined as the time from randomization to the time of documented disease progression, as determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria or death due to any cause. PFS distributions will be evaluated for each arm and will be graphically and quantitatively compared using Kaplan-Meier methods. These methods will be used to estimate the median PFS as well as 2-, 3-, and 5-year estimates for PFS by treatment arm along with corresponding 95% confidence intervals. Cox proportional hazards models will also be used to assess influential factors on PFS both in the univariate and the multivariable settings.

  assessed up to 10 years

Secondary Outcomes (16)

• Progression free survival (PFS) by local review

  up to 10 years

• Incidence of adverse events (AEs)

  Up to 30 days after last dose of study treatment

• Overall survival (OS)

  up to 10 years

• Objective response rate (ORR) by blinded independent central review (BICR)

  up to 10 years

• Complete response (CR) + partial response (PR) rate by blinded independent central review (BICR)

  up to 10 years

Other Outcomes (4)

• Health related quality of life

  up to 3 years

• Symptom burden

  up to 3 years

• Correlation of tumor genotype with PFS

  up to 10 years

Study Arms (2)

Arm I (temozolomide, placebo)

PLACEBO COMPARATOR

Patients receive IMRT/VMAT or PBS or IMPT QD on Monday-Friday for 33 fractions. Starting 4 weeks after radiotherapy, patients receive temozolomide PO QD on days 1-5 and placebo PO QD on days 1-28 of each cycle. Cycles of combination treatment repeat every 28 days for up to 12 months and placebo alone repeats every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and MRI throughout the study.

Radiation: Intensity-Modulated Radiation Therapy; Radiation: Volume Modulated Arc Therapy; Radiation: Pencil Beam Scanning; Procedure: Intensity-Modulated Proton Therapy; Drug: Temozolomide; Drug: Placebo Administration; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration

Arm II (temozolomide, vorasidenib)

EXPERIMENTAL

Patients receive IMRT/VMAT or PBS or IMPT QD on Monday-Friday for 33 fractions. Starting 4 weeks after radiotherapy, patients receive temozolomide PO QD on days 1-5 and vorasidenib PO QD on days 1-28 of each cycle. Cycles of combination treatment repeat every 28 days for up to 12 months and vorasidenib alone repeats every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and MRI throughout the study.

Radiation: Intensity-Modulated Radiation Therapy; Radiation: Volume Modulated Arc Therapy; Radiation: Pencil Beam Scanning; Procedure: Intensity-Modulated Proton Therapy; Drug: Temozolomide; Drug: Vorasidenib; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration

Interventions

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT/VMAT

Also known as: IMRT

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Volume Modulated Arc Therapy RADIATION

Undergo IMRT/VMAT

Also known as: VMAT

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Pencil Beam Scanning RADIATION

Undergo PBS

Also known as: PBS

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Intensity-Modulated Proton Therapy PROCEDURE

Undergo IMPT

Also known as: IMPT

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Temozolomide DRUG

Given PO

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Vorasidenib DRUG

Given PO

Arm II (temozolomide, vorasidenib)

Placebo Administration DRUG

Given PO

Arm I (temozolomide, placebo)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Questionnaire Administration OTHER

Ancillary Studies

Arm I (temozolomide, placebo); Arm II (temozolomide, vorasidenib)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• STEP 0: Histologic diagnosis of astrocytoma, IDH-mutant (central nervous system \[CNS\] WHO grade 3)
• STEP 0: Available diagnostic slides (hematoxylin and eosin staining method \[H\&E\] and immunohistochemical stains for central review)
• STEP 0: Tissue available for central biomarker testing (CDKN2A/B and1p/19q co-deletion \[all patients\], and IDH1/IDH2 \[if needed\])
• STEP 1: Centrally-confirmed diagnosis of astrocytoma, IDH-mutant (CNS WHO grade 3)
• STEP 1: Presence of IDH1 p.R132 or IDH2 p.172 mutation, confirmed by central review of immunohistochemical stain or molecular testing results, with central confirmation of equivocal results
• STEP 1: Absence of CDKN2A/B homozygous deletion by central testing
• STEP 1: Absence of whole arm 1p/19q co-deletion (i.e. intact 1p/19q) by central testing
• STEP 1: No evidence of spinal or leptomeningeal disease
• STEP 1: No prior chemotherapy, cranial irradiation, IDH-inhibitor therapy, radiotherapy, vaccine therapy, small-molecule therapy, or laser ablation
• STEP 1: Prior diagnostic surgery/resection/biopsy ≤ 6 months of registration
• STEP 1: Planned radiotherapy and adjuvant chemotherapy
• STEP 1: Age ≥ 12 years
• STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky performance status \[KPS\] ≥ 60%)
• STEP 1: Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
• STEP 1: Hemoglobin ≥ 9 g/dL

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Astrocytoma; Lymphoma, Follicular

Interventions

Radiotherapy, Intensity-Modulated; Temozolomide; vorasidenib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Ugonma N Chukwueke, MD

  Alliance for Clinical Trials in Oncology

  STUDY CHAIR

• Rifaquat M. Rahman, MD

  Alliance for Clinical Trials in Oncology

  STUDY CHAIR

• Patrick Y Wen, MD

  Alliance for Clinical Trials in Oncology

  STUDY CHAIR

Central Study Contacts

Alexandra Alexandra LeVasseur

CONTACT

773-834-4518; alevasseur@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2025
• First Posted: October 14, 2025
• Study Start: October 20, 2025
• Primary Completion (Estimated): May 31, 2033
• Study Completion (Estimated): January 1, 2040
• Last Updated: October 14, 2025

Record last verified: 2025-10