Astrocytoma, IDH-Mutant, Grade 3Phase 3NCT07215910
Testing Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer
A Phase 3 study testing Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy and Pencil Beam Scanning in people with Astrocytoma, IDH-Mutant, Grade 3, run by Alliance for Clinical Trials in Oncology at 177 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Astrocytoma, IDH-Mutant, Grade 3
- What is being tested?
- Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy and Pencil Beam Scanning
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 408 participants
- Where
- 177 sitesUnited States
- Study dates
- 24 Jun 2026to Jan 2040
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- -
Trial locations and contacts
177 sites in 1 country. Contact the study team or a site near you to ask about taking part.
177 sites in 1 country
United States177 sites, 176 recruiting
- Recruiting
Kaiser Permanente-Anaheim
Anaheim, California, 92806
Site Public Contact, 800-398-3996, clinical.trials@kp.org
Richard M. Green
- Recruiting
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Site Public Contact, 800-865-1125, CancerAnswerLine@med.umich.edu
Denise O. Leung
- Recruiting
Augusta University Medical Center
Augusta, Georgia, 30912
Site Public Contact, 706-721-2388, ga_cares@augusta.edu
Gerald C. Wallace
- Recruiting
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, 93301
Site Public Contact, 661-323-4673
Luis Mariscal
- Recruiting
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Site Public Contact, 212-639-7592
Lauren R. Schaff
- Recruiting
MaineHealth Coastal Cancer Treatment Center
Bath, Maine, 04530
Site Public Contact, 773-702-9171, protocols@AllianceNCTN.org
Christine Lu-Emerson
- Recruiting
Northwell Health Imbert Cancer Center
Bay Shore, New York, 11706
Site Public Contact, 516-734-8896
Samuel Singer
- Recruiting
Kaiser Permanente-Bellflower
Bellflower, California, 90706
Site Public Contact, 800-398-3996, clinical.trials@kp.org
Richard M. Green
- Recruiting
OSF Saint Joseph Medical Center
Bloomington, Illinois, 61701
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Tufts Medical Center
Boston, Massachusetts, 02111
Site Public Contact, 617-636-5000, ContactUsCancerCenter@TuftsMedicalCenter.org
Soma Sengupta
- Recruiting
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Site Public Contact, 877-726-5130
Julie J. Miller
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Site Public Contact, 877-442-3324
Ugonma N. Chukwueke
- Recruiting
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan, 48116
Site Public Contact, 800-865-1125
Denise O. Leung
- Recruiting
NYU Langone Hospital - Brooklyn
Brooklyn, New York, 11220
Site Public Contact, 646-754-4624, david.wallach@nyulangone.org
Jose R. McFaline Figueroa
- Recruiting
University of Vermont Medical Center
Burlington, Vermont, 05401
Site Public Contact, 802-656-4101, rpo@uvm.edu
Alissa A. Thomas
- Recruiting
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Site Public Contact, 802-656-8990, rpo@uvm.edu
Alissa A. Thomas
- Recruiting
Illinois CancerCare-Canton
Canton, Illinois, 61520
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Site Public Contact, 843-792-9321, hcc-clinical-trials@musc.edu
Sean Pennetti
- Recruiting
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
Site Public Contact, 312-226-2371, Cancer_Studies@rush.edu
Joo Yeon Nam
- Recruiting
University of Illinois
Chicago, Illinois, 60612
Site Public Contact, 312-355-3046
Stefania Maraka
- Recruiting
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Site Public Contact, 513-584-7698, cancer@uchealth.com
Lalanthica V. Yogendran
- Recruiting
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Milan G. Chheda
- Recruiting
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
Hamid R. Mohtashami
- Recruiting
Memorial Sloan Kettering Commack
Commack, New York, 11725
Site Public Contact, 212-639-7592
Lauren R. Schaff
- Recruiting
Mercy Hospital
Coon Rapids, Minnesota, 55433
Site Public Contact, 952-993-1517, mmcorc@healthpartners.com
Elizabeth C. Neil
- Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, 33065
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Milan G. Chheda
- Recruiting
Carle at The Riverfront
Danville, Illinois, 61832
Site Public Contact, 800-446-5532, Research@Carle.com
Maria T. Grosse-Perdekamp
- Recruiting
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Site Public Contact, 515-241-6727
Seema Harichand-Herdt
- Recruiting
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Broadlawns Medical Center
Des Moines, Iowa, 50314
Site Public Contact, 515-282-2200
Seema Harichand-Herdt
- Recruiting
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
Site Public Contact, 515-241-3305
Richard L. Deming
- Recruiting
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, 33166
Site Public Contact, kginnity@med.miami.edu
Macarena I. De La Fuente
- Recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Site Public Contact, 800-826-4673, becomingapatient@coh.org
Keng Lam
- Recruiting
Kaiser Permanente Dublin
Dublin, California, 94568
Site Public Contact, 877-642-4691
Donna Molaie
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Site Public Contact, 888-275-3853
Katherine B. Peters
- Recruiting
Fairview Southdale Hospital
Edina, Minnesota, 55435
Site Public Contact, 952-993-1517, mmcorc@healthpartners.com
Elizabeth C. Neil
- Recruiting
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Site Public Contact, 800-446-5532, Research@carle.com
Maria T. Grosse-Perdekamp
- Recruiting
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505
Site Public Contact, 412-864-7716, ClinicalResearchServices@upmc.edu
Michal Nisnboym Ziv
- Recruiting
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Site Public Contact, 847-570-2109
Christopher R. Trevino
- Recruiting
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Site Public Contact, 970-297-6150
Denise M. Damek
- Recruiting
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528
Site Public Contact, 773-702-9171, protocols@AllianceNCTN.org
Denise M. Damek
- Recruiting
Kaiser Permanente-Fremont
Fremont, California, 94538
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, 93720
Site Public Contact, 833-574-2273
Donna Molaie
- Recruiting
Kaiser Permanente-Fresno
Fresno, California, 93720
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026
Site Public Contact, 847-570-2109
Christopher R. Trevino
- Recruiting
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Suspended
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
- Recruiting
UCHealth Greeley Hospital
Greeley, Colorado, 80631
Site Public Contact, 773-702-9171, protocols@AllianceNCTN.org
Denise M. Damek
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Site Public Contact, 551-996-2897
Deric M. Park
- Recruiting
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Site Public Contact, 212-639-7592
Lauren R. Schaff
- Recruiting
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035
Site Public Contact, 847-570-2109
Christopher R. Trevino
- Recruiting
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, 33021
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Site Public Contact, 713-798-1354, burton@bcm.edu
Pushan R. Dasgupta
- Recruiting
Ben Taub General Hospital
Houston, Texas, 77030
Site Public Contact, 713-873-2000
Pushan R. Dasgupta
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Xiao-Tang Kong
- Recruiting
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Site Public Contact, 601-815-6700
Mark D. Anderson
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116
Site Public Contact, 913-588-3671
Tolga Tuncer
- Recruiting
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
Site Public Contact, 516-734-8896
Samuel Singer
- Recruiting
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Site Public Contact, 785-505-2800, Stephanie.Norris@LMH.ORG
Tolga Tuncer
- Recruiting
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Site Public Contact, 800-639-6918, cancer.research.nurse@dartmouth.edu
Kelli Pointer
- Recruiting
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
Site Public Contact, 800-398-3996, clinical.trials@kp.org
Richard M. Green
- Recruiting
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
Site Public Contact, 502-562-3429
Guneet Sarai
- Recruiting
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245
Site Public Contact, 502-852-2755, ctoinfo@louisville.edu
Guneet Sarai
- Recruiting
Medical Center of the Rockies
Loveland, Colorado, 80538
Site Public Contact, 970-203-7083
Denise M. Damek
- Recruiting
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Ankush Bhatia
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Ankush Bhatia
- Recruiting
West Jefferson Medical Center
Marrero, Louisiana, 70072
Site Public Contact, 504-210-3539, emede1@lsuhsc.edu
Yazmin Odia
- Recruiting
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Site Public Contact, 800-446-5532, Research@carle.com
Maria T. Grosse-Perdekamp
- Recruiting
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051
Site Public Contact, 262-257-5100
Jennifer M. Connelly
- Recruiting
East Jefferson General Hospital
Metairie, Louisiana, 70006
Site Public Contact, 504-210-3539, emede1@lsuhsc.edu
Yazmin Odia
- Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Site Public Contact, 212-639-7592
Lauren R. Schaff
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Site Public Contact, 414-805-3666
Jennifer M. Connelly
- Recruiting
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Site Public Contact, 212-263-4432, cancertrials@nyulangone.org
Jose R. McFaline Figueroa
- Recruiting
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Site Public Contact, 952-993-1517, mmcorc@healthpartners.com
Elizabeth C. Neil
- Recruiting
Kaiser Permanente- Modesto MOB II
Modesto, California, 95356
Site Public Contact, 877-642-4691
Donna Molaie
- Recruiting
Forbes Hospital
Monroeville, Pennsylvania, 15146
Site Public Contact, 412-858-7746
John Herbst
- Recruiting
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Site Public Contact, 212-639-7592
Lauren R. Schaff
- Recruiting
Morristown Medical Center
Morristown, New Jersey, 07960
Site Public Contact, 973-971-5900
Robert D. Aiken
- Recruiting
Northern Westchester Hospital
Mount Kisco, New York, 10549
Site Public Contact, 914-666-1366, AMellor@northwell.edu
Samuel Singer
- Recruiting
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, 53149
Site Public Contact, research.institute@phci.org
Timothy R. Wassenaar
- Recruiting
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151
Site Public Contact, 414-805-0505
Jennifer M. Connelly
- Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Nicholas A. Blondin
- Recruiting
University Medical Center New Orleans
New Orleans, Louisiana, 70112
Site Public Contact, 504-210-3539, emede1@lsuhsc.edu
Yazmin Odia
- Recruiting
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Site Public Contact, 504-894-5377
Yazmin Odia
- Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Site Public Contact, CancerTrials@nyulangone.org
Jose R. McFaline Figueroa
- Recruiting
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Maria Diaz Ordonez
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Site Public Contact, 212-639-7592
Lauren R. Schaff
- Recruiting
Helen F Graham Cancer Center
Newark, Delaware, 19713
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida, 33181
Site Public Contact, kginnity@med.miami.edu
Macarena I. De La Fuente
- Recruiting
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154
Site Public Contact, 414-805-0505
Jennifer M. Connelly
- Recruiting
Rush MD Anderson Cancer Center at Rush Oak Park
Oak Park, Illinois, 60304
Site Public Contact, 312-226-2371, Cancer_Studies@rush.edu
Joo Yeon Nam
- Recruiting
Kaiser Permanente-Oakland
Oakland, California, 94611
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066
Site Public Contact, 262-928-7878
Timothy R. Wassenaar
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Erika Santos Horta
- Recruiting
Kaiser Permanente-Ontario
Ontario, California, 91761
Site Public Contact, 800-398-3996, clinical.trials@kp.org
Richard M. Green
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Xiao-Tang Kong
- Recruiting
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
UI Healthcare Mission Cancer and Blood - Pella
Pella, Iowa, 50219
Site Public Contact, 515-282-2921, trials@missioncancer.com
Seema Harichand-Herdt
- Recruiting
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Peoria, Illinois, 61615
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Peru
Peru, Illinois, 61354
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Site Public Contact, 215-600-9151, ONCTrialNow@jefferson.edu
Nina L. Martinez
- Recruiting
Saint Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Site Public Contact, 877-602-4111
Yoshie Umemura
- Recruiting
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Site Public Contact, 877-284-2000
John Herbst
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-647-8073
Michal Nisnboym Ziv
- Recruiting
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-621-2334
Michal Nisnboym Ziv
- Recruiting
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
MaineHealth Maine Medical Center - Portland
Portland, Maine, 04102
Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org
Christine Lu-Emerson
- Recruiting
Providence Portland Medical Center
Portland, Oregon, 97213
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Alison K. Conlin
- Recruiting
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Alison K. Conlin
- Recruiting
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Inan Olmez
- Recruiting
Kaiser Permanente-Roseville
Roseville, California, 95661
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Kaiser Permanente Downtown Commons
Sacramento, California, 95814
Site Public Contact, 877-642-4691, kpoct@kp.org
Donna Molaie
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Site Public Contact, 916-734-3089
Orwa Aboud
- Recruiting
Kaiser Permanente-South Sacramento
Sacramento, California, 95823
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, 56303
Site Public Contact, 877-229-4907, coborncancercenter@centracare.com
Donald J. Jurgens
- Recruiting
Regions Hospital
Saint Paul, Minnesota, 55101
Site Public Contact, 952-993-1517, mmcorc@healthpartners.com
Elizabeth C. Neil
- Recruiting
United Hospital
Saint Paul, Minnesota, 55102
Site Public Contact, 952-993-1517, mmcorc@healthpartners.com
Elizabeth C. Neil
- Recruiting
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Site Public Contact, 888-424-2100, cancerinfo@hci.utah.edu
Joe S. Mendez
- Recruiting
Kaiser Permanente-San Francisco
San Francisco, California, 94115
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, 95119
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Kaiser Permanente San Leandro
San Leandro, California, 94577
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Kaiser San Rafael-Gallinas
San Rafael, California, 94903
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
MaineHealth Cancer Care Center of York County
Sanford, Maine, 04073
Site Public Contact, 207-459-1600
Christine Lu-Emerson
- Recruiting
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Kaiser Permanente-Santa Rosa
Santa Rosa, California, 95403
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074
Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org
Christine Lu-Emerson
- Recruiting
Swedish Medical Center-First Hill
Seattle, Washington, 98122
Site Public Contact, 206-215-2343, PCRC-NCORP@Swedish.org
Alison K. Conlin
- Recruiting
Kaiser Permanente-South San Francisco
South San Francisco, California, 94080
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Mercy Hospital Springfield
Springfield, Missouri, 65804
Site Public Contact, 417-269-4520
Jay W. Carlson
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Milan G. Chheda
- Recruiting
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Milan G. Chheda
- Recruiting
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Milan G. Chheda
- Recruiting
Stony Brook University Medical Center
Stony Brook, New York, 11794
Site Public Contact, 800-862-2215
Agnieszka Kowalska
- Recruiting
Overlook Hospital
Summit, New Jersey, 07902
Site Public Contact, 908-522-2043
Robert D. Aiken
- Recruiting
Tampa General Hospital
Tampa, Florida, 33606
Site Public Contact, 813-844-7829, syapchanyk@tgh.org
Sajeel A. Chowdhary
- Recruiting
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Nicholas A. Blondin
- Recruiting
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Site Public Contact, 212-639-7592
Lauren R. Schaff
- Recruiting
Carle Cancer Center
Urbana, Illinois, 61801
Site Public Contact, 800-446-5532, Research@carle.com
Maria T. Grosse-Perdekamp
- Recruiting
Kaiser Permanente-Vallejo
Vallejo, California, 94589
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
Kaiser Permanente-Walnut Creek
Walnut Creek, California, 94596
Site Public Contact, 877-642-4691, Kpoct@kp.org
Donna Molaie
- Recruiting
John Muir Medical Center-Walnut Creek
Walnut Creek, California, 94598
Site Public Contact, 925-941-4246, clinicalresearch@johnmuirhealth.com
Gigi Q. Chen
- Recruiting
Illinois CancerCare - Washington
Washington, Illinois, 61571
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Nicholas A. Blondin
- Recruiting
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188
Site Public Contact, 262-928-5539, Chanda.miller@phci.org
Timothy R. Wassenaar
- Recruiting
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095
Site Public Contact, 414-805-0505
Jennifer M. Connelly
- Recruiting
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Site Public Contact, 513-584-7698, cancer@uchealth.com
Lalanthica V. Yogendran
- Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, 15090
Site Public Contact, Dawnmarie.DeFazio@ahn.org
John Herbst
- Recruiting
University of Michigan Health - West
Wyoming, Michigan, 49519
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
Midwestern Regional Medical Center
Zion, Illinois, 60099
Site Public Contact, 844-793-0745
Laura Farrington
About this study
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
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.
Read the detailed description
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
- To determine if vorasidenib citrate (vorasidenib) and adjuvant temozolomide following radiation therapy improves progression-free survival (PFS) per blinded independent review in patients with newly-diagnosed IDH-mutant astrocytoma (World Health Organization [WHO] grade 3) compared to placebo given with adjuvant temozolomide following radiation therapy.
SECONDARY OBJECTIVES:
- To evaluate the safety and tolerability of vorasidenib versus (vs.) placebo in combination with temozolomide, following radiation therapy.
II. To evaluate PFS associated with vorasidenib vs. placebo in combination with temozolomide following radiation therapy, defined by local institutional review.
III. To evaluate the efficacy of vorasidenib vs. placebo in combination with adjuvant temozolomide, following radiation therapy, based on overall survival (OS).
IV. To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on objective response rate (ORR), complete response (CR) + partial response (PR), time to response, time to CR+PR, duration of response, and duration of CR+PR, with response assessed per the blinded independent review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria in patients with measurable tumor at baseline.
- To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on ORR, CR+PR, time to response, time to CR+PR, duration of response, and duration of CR+PR, with response assessed per local institutional review or investigator using the RANO 2.0 criteria.
VI. To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on time to next intervention.
VII. To evaluate vorasidenib vs. placebo in combination with temozolomide, following radiation, with respect to health-related quality of life (HRQoL) as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and symptom burden as assessed by the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT).
EXPLORATORY OBJECTIVES:
- To correlate tumor genotype with PFS. II. To evaluate the effect of the addition of vorasidenib to adjuvant temozolomide on seizure control.
OUTLINE: Patients are randomized 1:1 to 1 of 2 arms.
ARM I (CONTROL): Patients receive intensity-modulated radiation therapy (IMRT)/volume modulated arc therapy (VMAT) or pencil beam scanning (PBS) or intensity-modulated proton therapy (IMPT) once daily (QD) on Monday-Friday for 33 fractions. Starting 4 weeks after radiotherapy, patients receive temozolomide orally (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 magnetic resonance imaging (MRI) throughout the study.
ARM II (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.
After completion of study treatment, patients are followed up every 3 months for the first 2 years, every 4 months for the next 2 years, and then every 6 months for up to 10 years.
- Conditions
- Astrocytoma, IDH-Mutant, Grade 3
- Being tested
- Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy, Pencil Beam Scanning, Intensity-Modulated Proton Therapy, Temozolomide
- Medical subject headings
- Astrocytoma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT
Undergo IMRT/VMAT
Volume Modulated Arc TherapyRadiation
Also called VMAT
Undergo IMRT/VMAT
Pencil Beam ScanningRadiation
Also called PBS
Undergo PBS
Intensity-Modulated Proton TherapyProcedure or surgery
Also called IMPT
Undergo IMPT
TemozolomideDrug
Given PO
VorasidenibDrug
Given PO
Placebo AdministrationDrug
Given PO
Biospecimen CollectionProcedure or surgery
Undergo blood sample collection
Magnetic Resonance ImagingProcedure or surgery
Also called MRI
Undergo MRI
Questionnaire AdministrationOther
Ancillary Studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: assessed up to 10 years
Secondary outcomes (16)
Progression free survival (PFS) by local review
This is defined as the time from randomization to the time of documented disease progression, as determined by local (institutional/investigator) review 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.
Measured: up to 10 years
Incidence of adverse events (AEs)
AEs will be evaluated by treatment regimen. Will be summarized per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and where toxicities will be defined as AEs that are deemed to be at least possibly treatment-related. The maximum grade for each type of treatment-related AE will be recorded for each patient, and the frequency of each will be summarized by treatment arm. Frequency tables and graphical evaluations of AEs and treatment-related AEs will be summarized and evaluated to assess if there are any patterns or differences in the rates or types of AEs.
Measured: Up to 30 days after last dose of study treatment
Overall survival (OS)
This is defined as the time from randomization to the date of death due to any cause. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 2-, 3-, and 5-year rates along with corresponding 95% confidence intervals. Distributions will be compared between arms using the log rank test.
Measured: up to 10 years
Objective response rate (ORR) by blinded independent central review (BICR)
Will be summarized by treatment arm. This is defined as the proportion of patients with measurable tumor at baseline who achieve a minor, partial, or complete response to therapy divided by the total number of patients with measurable tumor at baseline who were randomized and treated on that arm. Response will be determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Assuming the number of patients who respond to therapy on each arm is binomially distributed, these proportions along with corresponding 95% confidence intervals will be estimated.
Measured: up to 10 years
Complete response (CR) + partial response (PR) rate by blinded independent central review (BICR)
Will be summarized by treatment arm. This is defined as the proportion of patients with measurable tumor at baseline who achieve a partial or complete response to therapy divided by the total number of patients with measurable tumor at baseline who were randomized and treated on that arm. Response will be determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Assuming the number of patients who respond to therapy on each arm is binomially distributed, these proportions along with corresponding 95% confidence intervals will be estimated.
Measured: up to 10 years
Time to response by blinded independent central review (BICR)
Will be summarized by treatment arm. This is defined only for patients with measurable disease at baseline as the time from randomization to the date of response to treatment (minor, partial, or complete), as determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 6- and 12-month rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Time to complete response (CR) + partial response (PR) by blinded independent central review (BICR)
Will be summarized by treatment arm. This is defined only for patients with measurable disease at baseline as the time from randomization to the date of response to treatment (partial or complete), as determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 6- and 12-month rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Duration of response by blinded independent central review (BICR)
Will be summarized by treatment arm for only patients who had measurable disease at baseline and achieved a response (minor, partial, or complete) while on treatment, as determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. This is defined as the time from the date of response to treatment (minor, partial, or complete) until the date of progression, as determined by BICR. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 1- and 2-year rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Duration of Complete response (CR) + partial response (PR) by blinded independent central review (BICR)
Will be summarized by treatment arm for only patients who had measurable disease at baseline and achieved a response (partial or complete) while on treatment, as determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. This is defined as the time from the date of response to treatment (partial or complete) until the date of progression, as determined by BICR. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 1- and 2-year rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Objective response rate (ORR) by local review
Will be summarized by treatment arm. This is defined as the proportion of patients with measurable tumor at baseline who achieve a minor, partial, or complete response to therapy divided by the total number of patients with measurable tumor at baseline who were randomized and treated on that arm. Response will be determined by local, institutional / investigator review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Assuming the number of patients who respond to therapy on each arm is binomially distributed, these proportions along with corresponding 95% confidence intervals will be estimated.
Measured: up to 10 years
Complete response (CR) + partial response (PR) rate by local review
Will be summarized by treatment arm. This is defined as the proportion of patients with measurable tumor at baseline who achieve a partial or complete response to therapy divided by the total number of patients with measurable tumor at baseline who were randomized and treated on that arm. Response will be determined by local, institutional / investigator review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Assuming the number of patients who respond to therapy on each arm is binomially distributed, these proportions along with corresponding 95% confidence intervals will be estimated.
Measured: up to 10 years
Time to response by local review
Will be summarized by treatment arm. This is defined only for patients with measurable disease at baseline as the time from randomization to the date of response to treatment (minor, partial, or complete), as determined by local, institutional / investigator review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 6- and 12-month rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Time to complete response (CR) + partial response (PR) by local review
Will be summarized by treatment arm. This is defined only for patients with measurable disease at baseline as the time from randomization to the date of response to treatment (partial or complete), as determined by local, institutional / investigator review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 6- and 12-month rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Duration of response by local review
Will be summarized by treatment arm for only patients who had measurable disease at baseline and achieved a response (minor, partial, or complete) while on treatment, as determined by local, institutional / investigator review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. This is defined as the time from the date of response to treatment (minor, partial, or complete) until the date of progression, as determined by local review. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 1- and 2-year rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Duration of Complete response (CR) + partial response (PR) by local review
Will be summarized by treatment arm for only patients who had measurable disease at baseline and achieved a response (partial or complete) while on treatment, as determined by local, institutional / investigator review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. This is defined as the time from the date of response to treatment (partial or complete) until the date of progression, as determined by local review. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 1- and 2-year rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Time to next therapeutic intervention
Will be summarized by treatment arm. This is defined as the time from randomization to the time of first subsequent non-protocol treatment. Distributions will be evaluated for each arm using the Kaplan Meier method to calculate 2-, 3-, and 5-year rates along with corresponding 95% confidence intervals.
Measured: up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2025
- Study start24 Jun 2026
- Primary completion31 May 2033 (estimated)
- Study completionJan 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Astrocytoma, IDH-Mutant, Grade 3Studies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 408 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ugonma N Chukwueke, MD, Study chair, Alliance for Clinical Trials in OncologyRifaquat M. Rahman, MD, Study chair, Alliance for Clinical Trials in OncologyPatrick Y Wen, MD, Study chair, Alliance for Clinical Trials in Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07215910
- Sponsor's protocol ID
- A072301
- Other IDs
- NCI-2025-04333
- Status last verified
- Nov 2026
- First submitted
- 9 Oct 2025
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07215910
- Acronym / sponsor ID
- A072301
- Conditions
- Astrocytoma, IDH-Mutant, Grade 3
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 408 participants (estimated)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 24 Jun 2026 (actual)
- Primary completion
- 31 May 2033 (estimated)
- Study completion
- Jan 2040 (estimated)
- First posted
- 14 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
- To determine if vorasidenib citrate (vorasidenib) and adjuvant temozolomide following radiation therapy improves progression-free survival (PFS) per blinded independent review in patients with newly-diagnosed IDH-mutant astrocytoma (World Health Organization [WHO] grade 3) compared to placebo given with adjuvant temozolomide following radiation therapy.
SECONDARY OBJECTIVES:
- To evaluate the safety and tolerability of vorasidenib versus (vs.) placebo in combination with temozolomide, following radiation therapy.
II. To evaluate PFS associated with vorasidenib vs. placebo in combination with temozolomide following radiation therapy, defined by local institutional review.
III. To evaluate the efficacy of vorasidenib vs. placebo in combination with adjuvant temozolomide, following radiation therapy, based on overall survival (OS).
IV. To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on objective response rate (ORR), complete response (CR) + partial response (PR), time to response, time to CR+PR, duration of response, and duration of CR+PR, with response assessed per the blinded independent review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria in patients with measurable tumor at baseline.
- To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on ORR, CR+PR, time to response, time to CR+PR, duration of response, and duration of CR+PR, with response assessed per local institutional review or investigator using the RANO 2.0 criteria.
VI. To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on time to next intervention.
VII. To evaluate vorasidenib vs. placebo in combination with temozolomide, following radiation, with respect to health-related quality of life (HRQoL) as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and symptom burden as assessed by the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT).
EXPLORATORY OBJECTIVES:
- To correlate tumor genotype with PFS. II. To evaluate the effect of the addition of vorasidenib to adjuvant temozolomide on seizure control.
OUTLINE: Patients are randomized 1:1 to 1 of 2 arms.
ARM I (CONTROL): Patients receive intensity-modulated radiation therapy (IMRT)/volume modulated arc therapy (VMAT) or pencil beam scanning (PBS) or intensity-modulated proton therapy (IMPT) once daily (QD) on Monday-Friday for 33 fractions. Starting 4 weeks after radiotherapy, patients receive temozolomide orally (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 magnetic resonance imaging (MRI) throughout the study.
ARM II (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.
After completion of study treatment, patients are followed up every 3 months for the first 2 years, every 4 months for the next 2 years, and then every 6 months for up to 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (temozolomide, placebo) | Placebo comparator | 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 AdministrationPatients 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. |
| Arm II (temozolomide, vorasidenib) | Experimental | 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 AdministrationPatients 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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (44 listed)
- 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
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intensity-Modulated Radiation TherapyAlso: IMRTUndergo IMRT/VMAT | Radiation | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
| Volume Modulated Arc TherapyAlso: VMATUndergo IMRT/VMAT | Radiation | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
| Pencil Beam ScanningAlso: PBSUndergo PBS | Radiation | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
| Intensity-Modulated Proton TherapyAlso: IMPTUndergo IMPT | Procedure or surgery | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
| TemozolomideGiven PO | Drug | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
| VorasidenibGiven PO | Drug | Arm II (temozolomide, vorasidenib) |
| Placebo AdministrationGiven PO | Drug | Arm I (temozolomide, placebo) |
| Biospecimen CollectionUndergo blood sample collection | Procedure or surgery | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
| Magnetic Resonance ImagingAlso: MRIUndergo MRI | Procedure or surgery | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
| Questionnaire AdministrationAncillary Studies | Other | Arm I (temozolomide, placebo), Arm II (temozolomide, vorasidenib) |
Primary outcome
Progression free survival (PFS) by blinded independent central review (BICR)
Time frame: assessed up to 10 years
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.
16 secondary outcomes
Progression free survival (PFS) by local review
Time frame: up to 10 years
Incidence of adverse events (AEs)
Time frame: Up to 30 days after last dose of study treatment
Overall survival (OS)
Time frame: up to 10 years
Objective response rate (ORR) by blinded independent central review (BICR)
Time frame: up to 10 years
Complete response (CR) + partial response (PR) rate by blinded independent central review (BICR)
Time frame: up to 10 years
Time to response by blinded independent central review (BICR)
Time frame: up to 10 years
Time to complete response (CR) + partial response (PR) by blinded independent central review (BICR)
Time frame: up to 10 years
Duration of response by blinded independent central review (BICR)
Time frame: up to 10 years
Duration of Complete response (CR) + partial response (PR) by blinded independent central review (BICR)
Time frame: up to 10 years
Objective response rate (ORR) by local review
Time frame: up to 10 years
Complete response (CR) + partial response (PR) rate by local review
Time frame: up to 10 years
Time to response by local review
Time frame: up to 10 years
Time to complete response (CR) + partial response (PR) by local review
Time frame: up to 10 years
Duration of response by local review
Time frame: up to 10 years
Duration of Complete response (CR) + partial response (PR) by local review
Time frame: up to 10 years
Time to next therapeutic intervention
Time frame: up to 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Astrocytoma, IDH-Mutant, Grade 3
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Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, Astrocytoma, Grade III
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ugonma N Chukwueke, MD study chair
Alliance for Clinical Trials in Oncology
Rifaquat M. Rahman, MD study chair
Alliance for Clinical Trials in Oncology
Patrick Y Wen, MD study chair
Alliance for Clinical Trials in Oncology
177 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy and Pencil Beam Scanning in people with Astrocytoma, IDH-Mutant, Grade 3, run by Alliance for Clinical Trials in Oncology at 177 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 44 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 177 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexandra Alexandra LeVasseur (773-834-4518, alevasseur@bsd.uchicago.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) by blinded independent central review (BICR) (time frame: assessed up to 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.