Trial Information

Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)

PRIMARY OBJECTIVES:

I. 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.

II. Compare failure-free survival (FFS) and overall survival of patients treated with these
regimens.

SECONDARY OBJECTIVES:

I. 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.

II. Compare the acute and late effects of VAC vs VAC alternating with VI, including the
toxicity associated with concurrent VI and radiotherapy.

III. Compare the acute and late effects of VAC as delivered on this study to that
administered on COG-D9803.

IV. 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.

V. Correlate UGT1A1 genotype with VI toxicity in patients receiving VAC alternating with VI.

VI. Correlate CYP2B6, CYP2C9, and GSTA1 genotypes with VAC toxicity. VII. 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.