Vor a sid en ib + temozolomide after radiation for IDH-mutant astrocytoma (grade 3)
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
Run by Alliance for Clinical Trials in Oncology · NCT07215910 · Data updated 2026-11-12
This phase 3 trial tests whether adding vorasidenib to the usual temozolomide after radiation helps people with newly diagnosed IDH-mutant astrocytoma (grade 3).
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Ages | 12 Years and up |
| Sex | All |
| Enrollment | 408 (estimated) |
| Sponsor | Alliance for Clinical Trials in Oncology Academic / other |
| Drugs / interventions | chemotherapy, prednisone, radiation |
| Locations | 177 sites (Phoenix, Arizona and 176 other locations) |
| Status | Recruiting |
| Started | June 24, 2026 |
| Main results expected | May 31, 2033 |
| Study ends | January 2040 |
| Registry record updated | November 3, 2026 |
| Trial ID | NCT07215910 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults with newly diagnosed IDH-mutant astrocytoma (WHO grade 3) after radiation who meet study biomarker and safety criteria.
✕Probably not a fit
Patients whose tumors do not respond to the combination or who experience intolerable side effects may not benefit.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
In this randomized, controlled study, participants receive vorasidenib plus temozolomide after completing radiation, or placebo plus temozolomide. The primary goal is to see if the combination improves progression-free survival compared with temozolomide alone. Secondary goals include safety, overall survival, and tumor response rates assessed by standard criteria. Eligibility requires confirmed IDH-mutant astrocytoma (grade 3) with no 1p/19q co-deletion and no prior cranial irradiation or IDH-inhibitor therapy. Treatment centers include several large institutions in Arizona and California.
Why it matters
Potential benefit: If successful, the regimen could delay tumor progression and potentially extend survival for patients with this brain cancer.
How similar studies have gone: Prior studies in similar IDH-mutant brain tumors have shown mixed results; this trial tests a targeted approach in a well-defined group.
Who can join: the full rules
Show full inclusion / exclusion criteria
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: \-
Where it's running
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Saint Joseph's Hospital and Medical Center
Phoenix, Arizona, United States Recruiting -
Kaiser Permanente-Anaheim
Anaheim, California, United States Recruiting -
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, United States Recruiting -
Kaiser Permanente-Bellflower
Bellflower, California, United States Recruiting -
City of Hope Comprehensive Cancer Center
Duarte, California, United States Recruiting -
Kaiser Permanente Dublin
Dublin, California, United States Recruiting
Show 44 more locations
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Kaiser Permanente-Fremont
Fremont, California, United States Recruiting -
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, United States Recruiting -
Kaiser Permanente-Fresno
Fresno, California, United States Recruiting -
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States Recruiting -
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, United States Recruiting -
Kaiser Permanente- Modesto MOB II
Modesto, California, United States Recruiting -
Kaiser Permanente-Oakland
Oakland, California, United States Recruiting -
Kaiser Permanente-Ontario
Ontario, California, United States Recruiting -
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States Recruiting -
Kaiser Permanente-Roseville
Roseville, California, United States Recruiting -
Kaiser Permanente Downtown Commons
Sacramento, California, United States Recruiting -
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States Recruiting -
Kaiser Permanente-South Sacramento
Sacramento, California, United States Recruiting -
Kaiser Permanente-San Francisco
San Francisco, California, United States Recruiting -
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, United States Recruiting -
Kaiser Permanente San Leandro
San Leandro, California, United States Recruiting -
Kaiser San Rafael-Gallinas
San Rafael, California, United States Recruiting -
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, United States Recruiting -
Kaiser Permanente-Santa Rosa
Santa Rosa, California, United States Recruiting -
Kaiser Permanente-South San Francisco
South San Francisco, California, United States Recruiting -
Kaiser Permanente-Vallejo
Vallejo, California, United States Recruiting -
Kaiser Permanente-Walnut Creek
Walnut Creek, California, United States Recruiting -
John Muir Medical Center-Walnut Creek
Walnut Creek, California, United States Recruiting -
Poudre Valley Hospital
Fort Collins, Colorado, United States Recruiting -
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, United States Recruiting -
UCHealth Greeley Hospital
Greeley, Colorado, United States Recruiting -
Medical Center of the Rockies
Loveland, Colorado, United States Recruiting -
Yale University
New Haven, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, United States Recruiting -
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, United States Recruiting -
Helen F Graham Cancer Center
Newark, Delaware, United States Recruiting -
Medical Oncology Hematology Consultants PA
Newark, Delaware, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, United States Recruiting -
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States Recruiting -
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States Recruiting -
Tampa General Hospital
Tampa, Florida, United States Recruiting -
Augusta University Medical Center
Augusta, Georgia, United States Recruiting -
OSF Saint Joseph Medical Center
Bloomington, Illinois, United States Recruiting
+127 more sites. See ClinicalTrials.gov for the full list.
Study contacts
- Study coordinator: Alexandra Alexandra LeVasseur
- Email: alevasseur@bsd.uchicago.edu
- Phone: 773-834-4518
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Safusidenib in IDH1-mutant glioma after vorasidenib progression
This trial tests safusidenib in people with IDH1-mutant glioma who progressed on vorasidenib and did not need immediate chemo or radiation.
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Retifanlimab With or Without DFMO for Progressive High-Grade Gliomas
This trial tests whether retifanlimab, with or without DFMO, is safe and may help treat progressive high-grade gliomas in adults.
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Safusidenib as maintenance therapy for IDH1‑mutant astrocytoma and oligodendroglioma
This trial tests whether the oral drug safusidenib can help people with IDH1‑mutant astrocytomas or oligodendrogliomas remain progression‑free longer after surgery and standard radiation/chemotherapy.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.