RECRUITING Phase 3 ClinicalTrials.gov

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)

Sponsor: Children's Oncology Group • ClinicalTrials.gov ID: NCT07466316

Registry updated: 2026-08-25

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Description

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.

Interventions

Biospecimen Collection (Procedure)
Undergo blood and cerebrospinal fluid sample collection
Bone Marrow Aspiration (Procedure)
Undergo bone marrow aspiration
Bone Marrow Biopsy (Procedure)
Undergo bone marrow biopsy
Bone Scan (Procedure)
Undergo bone scan
Computed Tomography (Procedure)
Undergo CT scan
Cyclophosphamide (Drug)
Given IV and PO
Dactinomycin (Biological)
Given IV
Irinotecan Hydrochloride (Drug)
Given IV
Lumbar Puncture (Procedure)
Undergo lumbar puncture
Lymph Node Biopsy (Procedure)
Undergo lymph node biopsy
Magnetic Resonance Imaging (Procedure)
Undergo MRI
Positron Emission Tomography (Procedure)
Undergo FDG PET scan
Radiation Therapy (Radiation)
Undergo radiation therapy
Resection (Procedure)
Undergo resection surgery
Survey Administration (Other)
Ancillary studies
Vincristine Sulfate (Drug)
Given IV
Vinorelbine Tartrate (Drug)
Given IV

Eligibility criteria

Inclusion Criteria: * 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) * 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 Exclusion Criteria: * 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) * 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

Conditions

Rhabdomyosarcoma

Locations

Children's Hospital of Alabama — Birmingham, Alabama, United States
USA Health Strada Patient Care Center — Mobile, Alabama, United States
Arkansas Children's Hospital — Little Rock, Arkansas, United States
City of Hope Comprehensive Cancer Center — Duarte, California, United States
Loma Linda University Medical Center — Loma Linda, California, United States
Cedars-Sinai Medical Center — Los Angeles, California, United States
Mattel Children's Hospital UCLA — Los Angeles, California, United States
Valley Children's Hospital — Madera, California, United States
Kaiser Permanente-Oakland — Oakland, California, United States
Children's Hospital of Orange County — Orange, California, United States
Children's Hospital Colorado — Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center — Denver, Colorado, United States
Connecticut Children's Medical Center — Hartford, Connecticut, United States
Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
Golisano Children's Hospital of Southwest Florida — Fort Myers, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital — Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville — Jacksonville, Florida, United States
Nemours Children's Hospital — Orlando, Florida, United States
Nemours Children's Clinic - Pensacola — Pensacola, Florida, United States
Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States
Saint Mary's Medical Center — West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
University of Illinois — Chicago, Illinois, United States
Riley Hospital for Children — Indianapolis, Indiana, United States
Blank Children's Hospital — Des Moines, Iowa, United States
Wesley Medical Center — Wichita, Kansas, United States
University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States
Norton Children's Hospital — Louisville, Kentucky, United States
MaineHealth Coastal Cancer Treatment Center — Bath, Maine, United States
MaineHealth Maine Medical Center - Portland — Portland, Maine, United States
MaineHealth Cancer Care Center of York County — Sanford, Maine, United States
Maine Children's Cancer Program — Scarborough, Maine, United States
MaineHealth Maine Medical Center- Scarborough — Scarborough, Maine, United States
Sinai Hospital of Baltimore — Baltimore, Maryland, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
UMass Memorial Medical Center - University Campus — Worcester, Massachusetts, United States
Bronson Battle Creek — Battle Creek, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital — Grand Rapids, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital — Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital — Grand Rapids, Michigan, United States
Bronson Methodist Hospital — Kalamazoo, Michigan, United States
West Michigan Cancer Center — Kalamazoo, Michigan, United States
Beacon Kalamazoo — Kalamazoo, Michigan, United States
Trinity Health Muskegon Hospital — Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital — Niles, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores — Norton Shores, Michigan, United States
Corewell Health Reed City Hospital — Reed City, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center — Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital — Saint Joseph, Michigan, United States
Munson Medical Center — Traverse City, Michigan, United States
University of Michigan Health - West — Wyoming, Michigan, United States
University of Mississippi Medical Center — Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
Mercy Hospital Saint Louis — St Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha — Omaha, Nebraska, United States
University of Nebraska Medical Center — Omaha, Nebraska, United States
Renown Regional Medical Center — Reno, Nevada, United States
Albany Medical Center — Albany, New York, United States
University of Rochester — Rochester, New York, United States
Montefiore Medical Center - Moses Campus — The Bronx, New York, United States
Mission Hospital — Asheville, North Carolina, United States
Children's Hospital Medical Center of Akron — Akron, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital — Toledo, Ohio, United States
Legacy Emanuel Children's Hospital — Portland, Oregon, United States
Lehigh Valley Hospital-Cedar Crest — Allentown, Pennsylvania, United States
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children — Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
Rhode Island Hospital — Providence, Rhode Island, United States
East Tennessee Childrens Hospital — Knoxville, Tennessee, United States
The Children's Hospital at TriStar Centennial — Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas — Austin, Texas, United States
Driscoll Children's Hospital — Corpus Christi, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas — Dallas, Texas, United States
Methodist Children's Hospital of South Texas — San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States
Primary Children's Hospital — Salt Lake City, Utah, United States
University of Virginia Cancer Center — Charlottesville, Virginia, United States
Inova Fairfax Hospital — Falls Church, Virginia, United States
Children's Hospital of The King's Daughters — Norfolk, Virginia, United States
Seattle Children's Hospital — Seattle, Washington, United States
Mary Bridge Children's Hospital and Health Center — Tacoma, Washington, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center — Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States
Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States
Centre Hospitalier Universitaire Sainte-Justine — Montreal, Quebec, Canada

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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