Vincristine, Dactinomycin, and Cyclophosphamide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma

PRIMARY OBJECTIVES:

I. Determine the failure-free survival of patients with newly diagnosed low-risk
rhabdomyosarcoma treated with vincristine (V), dactinomycin (A), cyclophosphamide (C), and
radiotherapy.

SECONDARY OBJECTIVES:

I. Determine local control rates in patients treated with this regimen. II. Determine the
rate of second-look surgery in patients with bulk residual tumor at diagnosis (clinical
group III) and the proportion of second-look surgeries that render patients treated with
this regimen tumor-free or with microscopic tumor only and evaluate the pathologic
significance of that residual tumor.

III. Determine the local control rates in patients with clinical group III disease treated
with response-adjusted radiotherapy doses after second-look surgical resection.

OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2
treatment regimens according to disease stage and clinical group.

REGIMEN I (subset 1 patients) [closed to accrual as of 08/13/2010: Patients receive VAC
chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-9 and dactinomycin
IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA
chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21 and
dactinomycin* IV over 1 minute on day 1 of weeks 13, 16, 19, and 22; and radiotherapy**, 5
days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed
dose.

REGIMEN II (subset 2 patients)[closed to accrual as of 9/23/2011]: Patients receive VAC
chemotherapy and radiotherapy** as in regimen I and VA chemotherapy comprising vincristine
IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin* IV over 1
minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46. Patients with
clinical group III disease may undergo second-look surgery at week 13 followed by
response-adjusted radiotherapy, and continued VA* chemotherapy. In both regimens, treatment
continues in the absence of disease progression or unacceptable toxicity.

NOTE: *For both regimens, dactinomycin is omitted during radiotherapy.

NOTE: **Clinical Group I tumors and those with Clinical Group III uterine/cervix primary
disease with negative nodes who have undergone a complete resection (i.e. hysterectomy) at
Week 13 do not receive radiotherapy at Week 13

Patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6
months for 1 year, and then annually thereafter.

Inclusion Criteria:

- Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid
or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting
criteria for 1 of the following subsets:

- Subset 1, defined by meeting 1 of the following criteria (closed to accrual as
of 08/13/2010):

- Stage 1 and clinical group I (completely resected) or II (microscopic
residual disease and/or regional lymph node involvement) disease

- Stage 1 and clinical group III (gross residual disease) disease arising in
the orbit

- Stage 2 and clinical group I or II disease

- Subset 2, defined by meeting 1 of the following criteria (closed to accrual as
of 09/23/2011):

- Stage 1 and clinical group III disease arising in a non-orbit site

- Stage 3 and clinical group I or II disease

- Prior staging ipsilateral retroperitoneal lymph node dissection required for all
patients age 10 and over with paratesticular tumors and patients under 10 years of
age with clinically or radiographically involved lymph nodes (except when extensive
lymph node involvement is identified by imaging studies)

- If there is extensive gross node involvement only confirmatory node biopsy is
recommended and the patient is classified as Clinical Group III

- Prior regional lymph node sampling required for patients with extremity tumors

- None of the following diagnoses:

- Intermediate-risk embryonal RMS

- Metastatic embryonal RMS

- Alveolar RMS

- Undifferentiated sarcoma

- RMS not otherwise specified (NOS)

- Other soft tissue sarcoma, including sarcoma NOS

- Prior enrollment on clinical trial COG-D9902

- Performance status - ECOG 0-2

- Performance status - Karnofsky 50-100% (≥ 16 years old)

- Performance status - Lansky 50-100% (< 16 years old)

- Absolute neutrophil count at least 750/mm^3

- Platelet count at least 75,000/mm^3 (transfusion independent)

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)*

- Creatinine* based on age/gender as follows:

- No greater than 0.8 mg/dL for patients age 5 and under

- No greater than 1.0 mg/dL for patients age 6 to 9

- No greater than 1.2 mg/dL for patients age 10 to 12

- No greater than 1.4 mg/dL for female patients age 13 and over

- No greater than 1.5 mg/dL for male patients age 13 to 15

- No greater than 1.7 mg/dL for male patients age 16 and over

- Creatinine clearance* or radioisotope glomerular filtration rate at least 70
mL/min/1.73 m^2

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled infection

- No prior chemotherapy (except for patients treated on the related intermediate-risk
study)

- Prior steroids allowed

- No prior radiotherapy