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RECRUITING

NCT07215910

PHASE3

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

Sponsor: Alliance for Clinical Trials in Oncology

View on ClinicalTrials.gov

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.

Official title: Phase III Trial of Radiotherapy Followed by Adjuvant Temozolomide in Combination With the IDH Inhibitor Vorasidenib vs Placebo in IDH-Mutated Newly-Diagnosed Grade 3 Astrocytomas

Key Details

Gender

All

Age Range

12 Years - Any

Study Type

INTERVENTIONAL

Enrollment

408

Start Date

2026-06-24

Completion Date

2040-01

Last Updated

2026-10-02

Healthy Volunteers

Conditions

Astrocytoma, IDH-Mutant, Grade 3

Interventions

RADIATION

Intensity-Modulated Radiation Therapy

Undergo IMRT/VMAT

RADIATION

Volume Modulated Arc Therapy

Undergo IMRT/VMAT

RADIATION

Pencil Beam Scanning

Undergo PBS

PROCEDURE

Intensity-Modulated Proton Therapy

Undergo IMPT

DRUG

Temozolomide

Given PO

DRUG

Vorasidenib

Given PO

DRUG

Placebo Administration

Given PO

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

OTHER

Questionnaire Administration

Ancillary Studies

Inclusion Criteria: * 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 * STEP 1: Platelet count ≥ 100,000/mm\^3 * STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) \* For patients with Gilbert syndrome, total bilirubin ≤ 1.0 x ULN * STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x ULN * STEP 1: Alkaline phosphatase ≤ 2.5 x ULN * STEP 1: Creatinine ≤ 2.0 x ULN or calculated (calc.) creatinine clearance \> 40 mL/min \* For patients ≥ 18 years of age, calculated using the Cockcroft-Gault equation. For patients \< 18 years of age, calculated using the Bedside Schwartz method: * Age: 10 to \< 13 years; Maximum Serum Creatinine (mg/dL): 1.2 (male) 1.2 (female) * Age: 13 to \< 16 years; Maximum Serum Creatinine (mg/dL): 1.5 (male) 1.4 (female) * Age: ≥ 16 years; Maximum Serum Creatinine (mg/dL): 1.7(male) 1.4 (female) * STEP 1: Not pregnant and not nursing, because this study involves agents whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown \* Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to registration is required * STEP 1: Women and men of reproductive potential should agree to abstain from sexual intercourse or use two highly effective methods of birth control, at least one of which must be a barrier method, throughout their participation in this study and for at least 90 days after the last dose of vorasidenib. Reproductive status and discussions about birth control measures should be documented in the patient's record. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of birth control. Highly effective forms of birth control are defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, intrauterine hormone release systems, bilateral tubal ligation, condoms with spermicide, or male partner sterilization * STEP 1: No severe or intercurrent illness, no active infection that requires systemic anti-infective therapy, and no active infection with an unexplained fever \> 38.5°C within 7 days prior to registration * STEP 1: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * STEP 1: Patients must be able to tolerate or undergo an MRI * STEP 1: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial * STEP 1: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * STEP 1: No significant active cardiac disease within 6 months prior to registration, including New York Heart Association Functional Classification class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke. To be eligible for this trial, patients should be class 2B or better * STEP 1: No history of significant (grade ≥ 2) intratumoral or peri-tumoral hemorrhage * STEP 1: No known active inflammatory gastrointestinal disease, chronic diarrhea, prior gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition causing an inability to swallow oral formulations of agents. Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential) * STEP 1: No known hypersensitivity to any of the components of vorasidenib or temozolomide * STEP 1: No other acute or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation or protocol therapy administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study * STEP 1: No concurrent use of other investigational agents * STEP 1: No concurrent use of alternating tumor treating field (TTField) therapy * STEP 1: No concurrent use of therapeutic doses of steroids for glioma. Concurrent use of physiologic doses of steroids (defined as equivalent of ≤ 10 mg prednisone daily) for medical conditions unrelated to glioma is allowed. Corticosteroids administered for reasons related to glioma should be used in the smallest dose possible to control symptoms of cerebral edema and mass effect and discontinued whenever possible. * STEP 1: No concurrent use of warfarin sodium or any other Coumadin-derivative anticoagulant. Patients must be off Coumadin-derivative anticoagulants for at least 7 days prior to registration. Low molecular weight heparin (LMWH) and factor Xa inhibitors are allowed * STEP 1: No concurrent use of strong and moderate CYP1A2 inhibitors, moderate CYP1A2 inducers, or CYP3A substrates where a minimal concentration change can reduce efficacy. Patients should be transferred to other medications prior to registration Exclusion Criteria: \-

Locations (152)

AIS Cancer Center at San Joaquin Community Hospital

Bakersfield, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Kaiser Permanente Dublin

Dublin, California, United States

Kaiser Permanente-Fremont

Fremont, California, United States

Kaiser Permanente Fresno Orchard Plaza

Fresno, California, United States

Kaiser Permanente-Fresno

Fresno, California, United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States

Kaiser Permanente- Modesto MOB II

Modesto, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Kaiser Permanente-Roseville

Roseville, California, United States

Kaiser Permanente Downtown Commons

Sacramento, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

Kaiser Permanente San Leandro

San Leandro, California, United States

Kaiser San Rafael-Gallinas

San Rafael, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Kaiser Permanente-Vallejo

Vallejo, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States

Yale University

New Haven, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Helen F Graham Cancer Center

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

UM Sylvester Comprehensive Cancer Center at Coral Springs

Coral Springs, Florida, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, United States

UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

North Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Augusta University Medical Center

Augusta, Georgia, United States

OSF Saint Joseph Medical Center

Bloomington, Illinois, United States

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Illinois CancerCare-Canton

Canton, Illinois, United States

Illinois CancerCare-Carthage

Carthage, Illinois, United States

University of Illinois

Chicago, Illinois, United States

Illinois CancerCare-Eureka

Eureka, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

NorthShore University HealthSystem-Glenbrook Hospital

Glenview, Illinois, United States

NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois, United States

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

OSF Saint Francis Radiation Oncology at Peoria Cancer Center

Peoria, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Illinois CancerCare-Peru

Peru, Illinois, United States

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Illinois CancerCare - Washington

Washington, Illinois, United States

Midwestern Regional Medical Center

Zion, Illinois, United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, United States

Iowa Methodist Medical Center