- Compare the early response rates in patients with intermediate-risk rhabdomyosarcoma (RMS) treated with vincristine, dactinomycin, and cyclophosphamide (VAC) vs VAC alternating with vincristine and irinotecan hydrochloride (VI) in combination with radiotherapy.
- Compare failure-free survival (FFS) and overall survival of patients treated with these regimens.
- Compare FFS, local control, and survival of patients with intermediate-risk RMS treated with VAC and early (week 4) radiotherapy vs delayed (week 10) radiotherapy, using data from IRS-IV for historic comparison.
- Compare the acute and late effects of VAC vs VAC alternating with VI, including the toxicity associated with concurrent VI and radiotherapy.
- Compare the acute and late effects of VAC as delivered on this study to that administered on COG-D9803.
- Correlate change in fludeoxyglucose F^18 positron emission tomography (FDG-PET) maximum standard uptake value from week 1 to week 4 and 15 with FFS.
- Correlate UGT1A1 genotype with VI toxicity in patients receiving VAC alternating with VI.
- Correlate CYP2B6, CYP2C9, and GSTA1 genotypes with VAC toxicity.
- Prospectively evaluate and validate gene expression values with the intent to define the best diagnostic predictors and more powerful prognostic classifiers.
OUTLINE: This is a prospective, historic control, randomized, multicenter study. Patients are stratified according to histology, disease stage, and clinical group (group III, stage 2 or 3 embryonal rhabdomyosarcoma [RMS] vs group I, stage 1 alveolar RMS vs group II or III, stage 2 or 3 alveolar RMS). Patients are randomized to 1 of 2 treatment arms. within 42 days of initial surgery or biopsy.
- Arm I (VAC): Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40.
- Arm II (VAC/VI): Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients* in both arms also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4 (except patients with alveolar RMS rendered group I by amputation OR patients needing week 1 emergency radiotherapy for symptomatic spinal cord compression).
NOTE: *Individualized local control plan that deviates from protocol-mandated radiotherapy allowed for patients ≤ 24 months of age
After completion of study treatment, patients are followed periodically for ≥ 10 years.
PROJECTED ACCRUAL: A total of 486 patients will be accrued for this study.
- Histologically or cytologically confirmed rhabdomyosarcoma (RMS)
- Must be concurrently enrolled on COG-D9902 to confirm local histologic diagnosis
- Intermediate-risk disease, defined by 1 of the following surgicopathologic and staging criteria:
- Group III, stage 2 or 3 embryonal, botryoid, or spindle cell RMS
- Group III, stage 2 or 3 ectomesenchymoma
- Group I-III, stage 1-3 alveolar RMS
- Newly diagnosed disease
- Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) required for patients ≥ 10 years of age with paratesticular tumors and for patients < 10 years with clinically or radiographically involved lymph nodes
- Patients with extensive lymph node involvement, defined as ≥ 2 lymph nodes > 2 cm in dimension, identified by imaging studies, are not required to undergo SIRLND
- Regional lymph node sampling or sentinel lymph node procedure is required for histologic evaluation in patients with extremity tumors
- Has undergone initial surgery or biopsy within the past 42 days
- Must be able to undergo radiotherapy
- ECOG performance status (PS) 0-2 (Karnofsky PS 50-100% [≥ 16 years of age] or Lansky PS 50-100% [< 16 years of age])
- Absolute neutrophil count ≥ 750/mm^3
- Platelet count ≥ 75,000/mm^3 (transfusion independent)
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min (40 mL/min for infants < 1 year of age)
- Patients with urinary tract obstruction by tumor must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment
- No evidence of uncontrolled infection
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy* (excluding steroids)
- No prior radiotherapy*
- No concurrent aprepitant during treatment with cyclophosphamide NOTE: *Patients who received prior radiotherapy or chemotherapy while enrolled on COG-ARST0331 allowed
Last updated: 11/22/2012
NCT ID: NCT00354835