AzTrials
AzTrials

RhabdomyosarcomaPhase 3NCT07466316

A Study Comparing Higher Dose Chemotherapy Over a Shorter Amount of Time to Lower Dose Chemotherapy Plus Maintenance Over a Longer Amount of Time in Patients With Newly Diagnosed Intermediate-Risk Rhabdomyosarcoma (IR RMS)

A Phase 3 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Rhabdomyosarcoma, run by Children's Oncology Group at 87 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase III trial compares higher dose chemotherapy, with vincristine, dactinomycin and cyclophosphamide, over a shorter amount of time to lower dose chemotherapy plus maintenance, with vincristine, dactinomycin, cyclophosphamide, irinotecan and vinorelbine, over a longer amount of time, along with standard of care… Read more about this study

Who is it for?
Ages Up to 50 years
Conditions the study is for
Rhabdomyosarcoma
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
342 participants
Where
87 sitesin 2 countries
Study dates
14 Jul 2026to 31 Mar 2031
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 Up to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patient must be ≤ 50 years of age at the time of enrollment
  • Patients with newly diagnosed soft tissue RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study based upon FOXO1 fusion status, Stage, Intergroup Rhabdomyosarcoma Study (IRS) group, and age, as below. FOXO1 fusion status must be determined prior to enrollment. RMS types included under embryonal rhabdomyosarcoma (ERMS) include those which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (typical, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Classification of alveolar Rhabdomyosarcoma (ARMS) in the 2020 WHO Classification is the same as in the International Classification of Rhabdomyosarcoma (ICR) and includes classic and solid variants.
  • FOXO1 fusion negative (FN)
  • Stage 2/3, Group III
  • Stage 4, Group IV, < 10 years old
  • FOXO1 fusion positive (FP)
Show all 38Show fewer
  • Stages 1-3, Groups I-III
  • Disease/staging imaging studies, if applicable, must be obtained within 21 days prior to enrollment and start of protocol therapy (repeat if necessary)
  • FOXO1 status results must be available to enroll. All patients will undergo institutional pathology review and institutional FOXO1 fusion determination regardless of histology prior to enrollment. FOXO1 status may confirmed by cytogenetic, fluorescence in situ hybridization (FISH), or next generation sequencing techniques. FOXO1 fusion results should be SUBMITTED as an upload to RAVE at study enrollment because this information is required for randomization.
  • Please note the following:
  • Institutional PAX3 versus (vs.) PAX7 determination is not required but should be submitted if available. Institutional FOXO1 testing may be performed at a contract or commercial lab as long as reports can be submitted and uploaded to RAVE. Additional molecular pathology reports, including the MCI report, are not required but should be submitted if available.
  • Patients who are < 10 years old with distant metastatic disease (Stage 4) who have institutional molecular testing indicating fusion negative (FN) RMS but are later found to have fusion positive (FP) RMS by MCI or other testing will be considered to have metastatic FP disease and will go off study
  • Appropriate lymph node sampling based on primary site of disease is required
  • Patients must have a performance status of Lansky performance status score ≥ 50 for patients ≤ 16 years of age or Karnofsky performance status score ≥ 50 for patients > 16 years of age
  • Peripheral absolute neutrophil count (ANC) ≥ 750/μL (All laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated. Laboratory studies must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment. Laboratory tests need not be repeated if therapy starts within seven (7) days of their most recent prior assessment. If the result of a laboratory study that is repeated at any time post-enrollment and prior to the start of protocol therapy is outside the limits for eligibility, then the evaluation must be rechecked within 48 hours prior to initiating protocol therapy. The results of the recheck must be within the limits for eligibility to proceed. If the result of the recheck is outside the limits of eligibility, the patient may not receive protocol therapy and will be considered off protocol therapy.)
  • Platelet count ≥ 75,000/μL (All laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated. Laboratory studies must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment. Laboratory tests need not be repeated if therapy starts within seven (7) days of their most recent prior assessment. If the result of a laboratory study that is repeated at any time post-enrollment and prior to the start of protocol therapy is outside the limits for eligibility, then the evaluation must be rechecked within 48 hours prior to initiating protocol therapy. The results of the recheck must be within the limits for eligibility to proceed. If the result of the recheck is outside the limits of eligibility, the patient may not receive protocol therapy and will be considered off protocol therapy.)
  • For pediatric patients < 18 years of age:
  • A serum creatinine based on age/sex as follows:
  • 1 month to < 6 months: Maximum serum creatinine 0.4 mg/dL (male), 0.4 mg/dL (female)
  • 6 months to < 1 year: Maximum serum creatinine 0.5 mg/dL (male), 0.5 mg/dL (female)
  • 1 to < 2 years: Maximum serum creatinine 0.6 mg/dL (male), 0.6 mg/dL (female)
  • 2 to < 6 years: Maximum serum creatinine 0.8 mg/dL (male), 0.8 mg/dL (female)
  • 6 to < 10 years: Maximum serum creatinine 1 mg/dL (male), 1 mg/dL (female)
  • 10 to < 13 years: Maximum serum creatinine 1.2 mg/dL (male), 1.2 mg/dL (female)
  • 13 to < 16 years: Maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
  • ≥ 16 years: Maximum serum creatinine 1.7 mg/dL (male),1.4 mg/dL (female)
  • OR a 24-hour urine Creatinine clearance ≥ 50 mL/min/1.73 m^2
  • OR a glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
  • Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
  • Patients with an elevated serum creatinine due to obstructive hydronephrosis secondary to tumor are still eligible. However, patients with urinary tract obstruction by tumor must have unimpeded urinary flow established via diversion (ie, percutaneous nephrostomies or ureteric stents) of the urinary tract.
  • For adult patients (aged 18 years or older):
  • Creatinine clearance ≥ 50 mL/min, as estimated by the Cockcroft and Gault formula or as a 24-hour urine collection. Estimated creatinine clearance is based on actual body weight.
  • (All laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated. Laboratory studies must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment. Laboratory tests need not be repeated if therapy starts within seven (7) days of their most recent prior assessment. If the result of a laboratory study that is repeated at any time post-enrollment and prior to the start of protocol therapy is outside the limits for eligibility, then the evaluation must be rechecked within 48 hours prior to initiating protocol therapy. The results of the recheck must be within the limits for eligibility to proceed. If the result of the recheck is outside the limits of eligibility, the patient may not receive protocol therapy and will be considered off protocol therapy.)
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (All laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated. Laboratory studies must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment. Laboratory tests need not be repeated if therapy starts within seven (7) days of their most recent prior assessment. If the result of a laboratory study that is repeated at any time post-enrollment and prior to the start of protocol therapy is outside the limits for eligibility, then the evaluation must be rechecked within 48 hours prior to initiating protocol therapy. The results of the recheck must be within the limits for eligibility to proceed. If the result of the recheck is outside the limits of eligibility, the patient may not receive protocol therapy and will be considered off protocol therapy.)
  • If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 135 U/L (All laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated. Laboratory studies must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment. Laboratory tests need not be repeated if therapy starts within seven (7) days of their most recent prior assessment. If the result of a laboratory study that is repeated at any time post-enrollment and prior to the start of protocol therapy is outside the limits for eligibility, then the evaluation must be rechecked within 48 hours prior to initiating protocol therapy. The results of the recheck must be within the limits for eligibility to proceed. If the result of the recheck is outside the limits of eligibility, the patient may not receive protocol therapy and will be considered off protocol therapy.)
  • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.
  • Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Who cannot join

  • Patients with evidence of uncontrolled infection are not eligible
  • Previous or concurrent cancer(s) that is/was being treated with chemotherapy and/or radiation.
  • Note: Surgical resection alone of previous or concurrent cancer(s) is allowed
  • Patients with central nervous system involvement of RMS as defined below:
  • Malignant cells detected in cerebrospinal fluid
  • Intra-parenchymal brain metastases separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed)
Show all 14Show fewer
  • Diffuse leptomeningeal disease
  • Patients with known Charcot-Marie-Tooth disease
  • Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment. Note: the following exception:
  • Patients requiring emergency radiation therapy for life-threatening complications of tumor burden due to RMS. These patients are eligible, provided they are consented to ARST2531 prior to administration of radiation.
  • Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (eg, autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy
  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Trial locations and contacts

87 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

87 sites in 2 countries

United States86 sites, 85 recruiting

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

    Site Public Contact, 330-543-3193

    Erin Wright

    Recruiting

  • Albany Medical Center

    Albany, New York, 12208

    Site Public Contact, 518-262-5513

    Lauren R. Weintraub

    Recruiting

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

    Site Public Contact, 610-402-9543, Morgan_M.Horton@lvhn.org

    Jacob A. Troutman

    Recruiting

  • Mission Hospital

    Asheville, North Carolina, 28801

    Site Public Contact, 828-213-7055, NCDV.ResearchRegulatory@HCAHealthcare.com

    Douglas J. Scothorn

    Recruiting

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

    Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org

    Claire Stokes

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org

    Navin R. Pinto

    Recruiting

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

    Site Public Contact, 512-628-1902, TXAUS-DL-SFCHemonc.research@ascension.org

    Shannon M. Cohn

    Recruiting

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

    Site Public Contact, 410-601-9083

    Jason M. Fixler

    Recruiting

  • MaineHealth Coastal Cancer Treatment Center

    Bath, Maine, 04530

    Site Public Contact, 888-823-5923, ctsucontact@westat.com

    Ashley M. Jean

    Recruiting

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

    Site Public Contact, 205-638-9285, oncologyresearch@peds.uab.edu

    Jamie M. Aye

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Site Public Contact, 877-442-3324

    Natalie B. Collins

    Recruiting

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

    Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu

    Brian C. Belyea

    Recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

    Site Public Contact, 773-880-4562

    Jennifer L. Reichek

    Recruiting

  • University of Illinois

    Chicago, Illinois, 60612

    Site Public Contact, 312-355-3046

    Dipti S. Dighe

    Recruiting

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

    Site Public Contact, 361-694-5311, Crystal.DeLosSantos@dchstx.org

    Nkechi I. Mba

    Recruiting

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

    Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu

    Avanthi T. Shah

    Recruiting

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

    Site Public Contact, 303-832-2344, PSGResearchSharedMailbox@HCAHealthcare.com

    Florence Choo

    Recruiting

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

    Site Public Contact, 515-241-8912, samantha.mallory@unitypoint.org

    Samantha L. Mallory

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

    Site Public Contact, 800-826-4673, becomingapatient@coh.org

    Janet M. Yoon

    Recruiting

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

    Site Public Contact, 703-208-6650, Stephanie.VanBebber@inova.org

    Robin Y. Dulman

    Recruiting

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

    Site Public Contact, 239-343-5333, molly.arnstrom@leehealth.org

    Emad K. Salman

    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

    Recruiting

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

    Site Public Contact, 860-545-9981

    Michael S. Isakoff

    Recruiting

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

    Site Public Contact, 954-265-1847, OHR@mhs.net

    Iftikhar Hanif

    Recruiting

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

    Site Public Contact, 800-248-1199

    Marissa Just

    Recruiting

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

    Site Public Contact, 601-815-6700

    Amanda Strobel

    Recruiting

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Sridhi Patel

    Recruiting

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Beacon Kalamazoo

    Kalamazoo, Michigan, 49048

    Site Public Contact, 574-647-7370

    Kathleen Y. Butler

    Recruiting

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

    Site Public Contact, 816-302-6808, COGResearchGroup@cmh.edu

    Keith J. August

    Recruiting

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

    Site Public Contact, 865-541-8266

    Susan E. Spiller

    Recruiting

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

    Site Public Contact, 859-257-3379

    James T. Badgett

    Not yet recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

    Site Public Contact, 501-364-7373

    Michael W. Bishop

    Recruiting

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

    Site Public Contact, 909-558-4050

    Albert Kheradpour

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Site Public Contact, 310-423-2133, Cancer.trial.info@cshs.org

    Leo Mascarenhas

    Recruiting

  • Mattel Children's Hospital UCLA

    Los Angeles, California, 90095

    Site Public Contact, 310-825-6708

    Noah C. Federman

    Recruiting

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

    Site Public Contact, 502-629-5500, CancerResource@nortonhealthcare.org

    Michael J. Ferguson

    Recruiting

  • Valley Children's Hospital

    Madera, California, 93636

    Site Public Contact, 559-353-3000, Research@valleychildrens.org

    Ruetima Titapiwatanakun

    Recruiting

  • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

    Madison, Wisconsin, 53718

    Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Margo L. Hoover-Regan

    Recruiting

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

    Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Margo L. Hoover-Regan

    Recruiting

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

    Site Public Contact, 414-955-4727, MACCCTO@mcw.edu

    Angela Steineck

    Recruiting

  • USA Health Strada Patient Care Center

    Mobile, Alabama, 36604

    Site Public Contact, 800-388-8721

    Hamayun Imran

    Recruiting

  • Trinity Health Muskegon Hospital

    Muskegon, Michigan, 49444

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

    Site Public Contact, 615-342-1919

    Clinton M. Carroll

    Recruiting

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

    Site Public Contact, 616-391-1230

    Kathleen Y. Butler

    Recruiting

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

    Site Public Contact, 757-668-7243, CCBDCresearch@chkd.org

    Melissa S. Mark

    Recruiting

  • Cancer and Hematology Centers of Western Michigan - Norton Shores

    Norton Shores, Michigan, 49444

    Suspended

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

    Site Public Contact, 877-642-4691, Kpoct@kp.org

    Aarati V. Rao

    Recruiting

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

    Site Public Contact, 402-955-3949

    Jill C. Beck

    Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

    Site Public Contact, 402-559-6941, unmcrsa@unmc.edu

    Jill C. Beck

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, 92868

    Site Public Contact, 714-509-8646, oncresearch@choc.org

    Elyssa M. Rubin

    Recruiting

  • Nemours Children's Hospital

    Orlando, Florida, 32827

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Sridhi Patel

    Recruiting

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

    Site Public Contact, helpdesk@childrensoncologygroup.org

    Jeffrey H. Schwartz

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Site Public Contact, 267-425-5544, CancerTrials@email.chop.edu

    Jacquelyn Crane

    Recruiting

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

    Site Public Contact, 215-427-8991

    Gregory E. Halligan

    Recruiting

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

    Site Public Contact, 412-692-8570, jean.tersak@chp.edu

    Jessica Daley

    Recruiting

  • MaineHealth Maine Medical Center - Portland

    Portland, Maine, 04102

    Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org

    Ashley M. Jean

    Recruiting

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

    Site Public Contact, 503-413-2560

    Jason M. Glover

    Recruiting

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

    Site Public Contact, 401-444-1488

    Bradley DeNardo

    Recruiting

  • Corewell Health Reed City Hospital

    Reed City, Michigan, 49677

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Renown Regional Medical Center

    Reno, Nevada, 89502

    Site Public Contact, 775-982-5050, Renown-CRD@renown.org

    Seema L. Rao

    Recruiting

  • University of Rochester

    Rochester, New York, 14642

    Site Public Contact, 585-275-5830

    Rafi R. Kazi

    Recruiting

  • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Corewell Health Lakeland Hospitals - Saint Joseph Hospital

    Saint Joseph, Michigan, 49085

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

    Site Public Contact, 801-585-5270

    Matthew Dietz

    Recruiting

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

    Site Public Contact, 210-575-6240, Vinod.GidvaniDiaz@hcahealthcare.com

    Jose M. Esquilin

    Recruiting

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

    Site Public Contact, 210-450-3800, phoresearchoffice@uthscsa.edu

    Aaron J. Sugalski

    Recruiting

  • MaineHealth Cancer Care Center of York County

    Sanford, Maine, 04073

    Site Public Contact, 207-459-1600

    Ashley M. Jean

    Recruiting

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

    Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org

    Ashley M. Jean

    Recruiting

  • MaineHealth Maine Medical Center- Scarborough

    Scarborough, Maine, 04074

    Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org

    Ashley M. Jean

    Recruiting

  • Seattle Children's Hospital

    Seattle, Washington, 98105

    Site Public Contact, 866-987-2000

    Sarah E. Leary

    Recruiting

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

    Site Public Contact, 314-251-7066

    Robin D. Hanson

    Recruiting

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

    Site Public Contact, 727-767-4784, Ashley.Repp@jhmi.edu

    Blake Foxworthy

    Recruiting

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

    Site Public Contact, 253-403-1461, research@multicare.org

    Robert G. Irwin

    Recruiting

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Alice Lee

    Recruiting

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio, 43606

    Site Public Contact, 419-824-1842, PCIOncResearch@promedica.org

    Jamie L. Dargart

    Recruiting

  • Munson Medical Center

    Traverse City, Michigan, 49684

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Saint Mary's Medical Center

    West Palm Beach, Florida, 33407

    Site Public Contact, 561-822-4745

    Matthew D. Ramirez

    Recruiting

  • Wesley Medical Center

    Wichita, Kansas, 67214

    Site Public Contact, 316-962-7802, WesleyResearch@wesleymc.com

    Nathan S. Hall

    Recruiting

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Sridhi Patel

    Recruiting

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts, 01655

    Site Public Contact, 508-856-3216, cancer.research@umassmed.edu

    Stefanie R. Lowas

    Recruiting

  • University of Michigan Health - West

    Wyoming, Michigan, 49519

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

Other trials in United States

Canada1 site, 1 recruiting

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

    Site Public Contact, 514-345-4931, yvan.samson@umontreal.ca

    Monia Marzouki

    Recruiting

Other trials in Canada

About this study

Official title: A Randomized Phase 3 Study to Compare VAC (Higher Cyclophosphamide Dose and Intensity) Versus VAC/VI (Lower Cyclophosphamide Dose and Intensity) Plus Maintenance Therapy in Patients With Newly Diagnosed Intermediate-Risk Rhabdomyosarcoma

This phase III trial compares higher dose chemotherapy, with vincristine, dactinomycin and cyclophosphamide, over a shorter amount of time to lower dose chemotherapy plus maintenance, with vincristine, dactinomycin, cyclophosphamide, irinotecan and vinorelbine, over a longer amount of time, along with standard of care surgery and radiation, in patients with newly diagnosed intermediate risk rhabdomyosarcoma. Vincristine and vinorelbine are in a class of medications called vinca alkaloids. They work by stopping tumor cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's DNA and may kill tumor cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells. It may also lower the body's immune response. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. It is not yet known if the higher dose chemotherapy over a shorter amount of time or the lower dose chemotherapy with maintenance over a longer amount of time is more effective in the treatment of patient with newly diagnosed, intermediate risk rhabdomyosarcoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine if the event free survival (EFS) of patients with intermediate risk rhabdomyosarcoma (IR RMS) treated with surgery, radiotherapy, and vincristine, dactinomycin, cyclophosphamide (VAC) (2.2 g/m^2/cycle cyclophosphamide) chemotherapy (regimen A) is better than that of patients treated with surgery, radiotherapy, and VAC alternating with vincristine, irinotecan (VI) (VAC/VI) (1.2 g/m^2/cycle cyclophosphamide) chemotherapy plus 24 weeks of maintenance chemotherapy with vinorelbine and cyclophosphamide (regimen B).

SECONDARY OBJECTIVES:

  1. To determine if the overall survival (OS) of patients with IR RMS treated with surgery and/or radiotherapy, and VAC (2.2 g/m^2/cycle cyclophosphamide) chemotherapy (regimen A) is better than the OS of patients treated with surgery, radiotherapy, and VAC alternating with VI (VAC/VI) (1.2 g/m^2/cycle cyclophosphamide) plus 24 weeks of maintenance chemotherapy with vinorelbine and cyclophosphamide (regimen B).

II. To compare clinician-reported treatment-related adverse event (AE) rates between two regimens.

III. To determine what proportion of patients deemed eligible for delayed primary excision (DPE) on retrospective central review undergo DPE and to assess the concordance of DPE eligibility between the central review and local site.

IV. To compare the 4-year local failure (LF) rate of patients deemed DPE-eligible by retrospective central review who undergo DPE with the 4-year LF rate of patients deemed DPE-eligible by central review who do not undergo DPE.

  1. To determine the feasibility of reporting diagnostic tumor molecular features identified via the Molecular Characterization Initiative (MCI) within 6 weeks of treatment initiation for clinical group III patients.

EXPLORATORY OBJECTIVES:

  1. To prospectively evaluate the following somatic molecular features (PAX3 or PAX7 and FOXO1 fusion, MYCN amplification, TP53 mutation, MYOD1 mutation, CDK4 amplification) via MCI and determine their association with EFS and OS.

II. To explore the relationship between methylation patterns in IR RMS and EFS and OS.

III. To test the use of digital pathology/artificial intelligence to refine the diagnosis of IR RMS.

IV. To assess the differential impact of regimen intensity on gonadal toxicity experienced by patients.

  1. To determine the proportion of patients having fertility discussions and fertility preservation procedures prior to starting treatment.

VI. To collect biospecimens for patient-derived xenograft (PDX) RMS model generation.

VII. To bank biospecimens for future research. VIII. To evaluate the association between Household Material Hardship (HMH) measures and EFS and OS.

OUTLINE: Patients are randomized to 1 of 2 regimens.

REGIMEN A:

CYCLES 1-4, 8, 12: Patients receive vincristine intravenously (IV) on days 1, 8 and 15 of each cycle, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of each cycle, and cyclophosphamide IV over 1-6 hours on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

CYCLES 5, 9, 10, 13, 14: Patients receive vincristine IV on day 1 of each cycle, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of each cycle, and cyclophosphamide IV over 1-6 hours on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

CYCLE 6: Patients receive vincristine IV on day 1 and cyclophosphamide IV over 1-6 hours on day 1. Cycle 6 continues for 21 days in the absence of disease progression or unacceptable toxicity.

CYCLE 7: Patients receive vincristine IV on days 1, 8 and 15 and cyclophosphamide IV over 1-6 hours on day 1. Cycle 7 continues for 21 days in the absence of disease progression or unacceptable toxicity.

Patients may undergo surgical resection during cycle 4 (week 12), radiation to the primary site during cycle 5 and 6 and/or radiation to distant metastatic sites during cycle 14. Patients do not receive dactinomycin during radiation. Patients undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may undergo lymph node biopsy during screening and/or fludeoxyglucose (FDG) positron emission tomography (PET) scan, bone scan, bone marrow biopsy and aspiration, lumbar puncture with cerebrospinal fluid sample collection throughout the study.

REGIMEN B:

CYCLES 1, 3, 8: Patients receive vincristine IV on days 1, 8 and 15 of each cycle, dactinomycin IV over 15 or 10-15 minutes on day 1 of each cycle, and cyclophosphamide IV over 1-6 hours on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

CYCLES 2, 4, 11: Patients receive vincristine IV on days 1, 8 and 15 of each cycle and irinotecan IV over 90 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

CYCLES 5, 10, 12, 14: Patients receive vincristine IV on day 1 of each cycle, dactinomycin IV over 15 or 10-15 minutes on day 1 of each cycle, and cyclophosphamide IV over 1-6 hours on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

CYCLES 6, 7, 9, 13: Patients receive vincristine IV on days 1 and 8 of each cycle and irinotecan IV over 90 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients may undergo surgical resection during cycle 4 (week 12), radiation to the primary site during cycle 5 and 6 and/or radiation to distant metastatic sites during cycle 14. Patients do not receive dactinomycin during radiation.

MAINTENANCE: Patients receive vinorelbine IV over 6-10 minutes on days 1, 8 and 15 of each cycle and cyclophosphamide orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients undergo CT scan and/or MRI and blood sample collection throughout the study. Patients may undergo lymph node biopsy during screening and/or FDG PET scan, bone scan, bone marrow biopsy and aspiration, lumbar puncture with cerebrospinal fluid sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for years 2 and 3 then every 6 months for year 4 and 5.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Bone Scan, Computed Tomography
Medical subject headings
Rhabdomyosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood and cerebrospinal fluid sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV and PO

  • DactinomycinBiological

    Also called Actinomycin A IV, Actinomycin C1, Actinomycin D, Actinomycin I1

    Given IV

  • Irinotecan HydrochlorideDrug

    Also called Campto, Camptosar, Camptothecin 11, Camptothecin-11

    Given IV

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • Lymph Node BiopsyProcedure or surgery

    Also called Biopsy of Lymph Node

    Undergo lymph node biopsy

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo FDG PET scan

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

  • ResectionProcedure or surgery

    Also called Surgical Resection

    Undergo resection surgery

  • Survey AdministrationOther

    Ancillary studies

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

  • Vinorelbine TartrateDrug

    Also called Biovelbin, Eunades, KW 2307, KW-2307

    Given IV

Study groups in NCT07466316
Study groupRoleWhat they receive
Regimen A (Higher cyclophosphamide dose regimenExperimentalSee Detailed Description for Regimen A.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dactinomycin; Procedure: Lumbar Puncture; Procedure: Lymph Node Biopsy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Procedure: Resection; Other: Survey Administration; Drug: Vincristine Sulfate
Regimen B (Lower cyclophosphamide dose, maintenance)ExperimentalSee Detailed Description for Regimen B.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dactinomycin; Drug: Irinotecan Hydrochloride; Procedure: Lumbar Puncture; Procedure: Lymph Node Biopsy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Procedure: Resection; Other: Survey Administration; Drug: Vincristine Sulfate; Drug: Vinorelbine Tartrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event free survival (EFS)

    Will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the stratified log-rank test.

    Measured: From randomization until the first occurrence of progression or relapse, second malignancy, or death, assessed up to 5 years

Secondary outcomes (5)

  1. Overall survival (OS)

    Will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the stratified log-rank test.

    Measured: From randomization to death from any cause, assessed up to 4 years

  2. Clinician-reported adverse events (AEs)

    Clinician-reported treatment-related grade 3 or higher AEs will be reported using Common Terminology Criteria for Adverse Events version 5.0. Comparison of toxicities will be conducted using Fisher's exact test. The maximum grade for each toxicity will be recorded for each patient. Averages and confidence intervals for these toxicity frequencies will be provided.

    Measured: Up to 5 years

  3. Proportion of patients undergoing delayed primary excision (DPE) among patients deemed to be DPE eligible on retrospective central review

    Eligibility for DPE will be established through a retrospective central review of diagnostic and pre-local control imaging. Among the patients deemed eligible for DPE, the proportion of those who undergo DPE will be determined along with 95% confidence interval. Cohen's kappa will be used to assess the concordance between site reviews and central reviews. 95% confidence of kappa statistics will be provided.

    Measured: Up to week 12 of treatment

  4. Local failure rate for patients deemed eligible for DPE

    Cumulative incidence curves will be used to present the local failure rates over time.

    Measured: Up to 5 years

  5. Percentage of molecular biomarker testing that is resulted within the 6-week timeframe

    Assessing the feasibility of reporting diagnostic tumor molecular features in patients with clinical group III intermediate risk rhabdomyosarcoma via the molecular characterization initiative (MCI) among the first 50 Clinical Group III patients who initiated treatment and consent to MCI. If 14 or more patients cannot have diagnostic tumor molecular features identified via MCI within 6 weeks of treatment, this aim will be considered not feasible.

    Measured: Up to cycle 3 (each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2026
  2. Study start14 Jul 2026
  3. Primary completion31 Mar 2031 (estimated)
  4. Study completion31 Mar 2031 (estimated)

Resources

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
None (open label)
Enrolment
342 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07466316
Sponsor's protocol ID
ARST2531
Other IDs
NCI-2026-00319, ARST2531, ARST2531, U10CA180886
Status last verified
Aug 2026
First submitted
28 Jan 2026
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Rhabdomyosarcoma, run by Children's Oncology Group at 87 sites in 2 countries.

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 38 inclusion and 14 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 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 87 sites in United States, Canada. 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. 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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event free survival (EFS) (time frame: From randomization until the first occurrence of progression or relapse, second malignancy, or death, assessed up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07466316.

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 25 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in