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

• Estimated Percentage of Patients Failure Free at 5 Years (95% Confidence Interval) [ Time Frame: 5 years from study enrollment ]
  Failure-free survival: Time to disease recurrence or death as a first event. An analysis plan based on the method of Woolson (1981) will be used to monitor outcome for these patients.
  
  
• Estimated Percentage of Patients With Stage 1, Clinical Group IIB or C (Node Positive) or Stage 2 Group I or Stage 2 Group II Disease Treated With Regimen 1 Failure-free at 5 Years [ Time Frame: 5 years from study enrollment ]
  Failure-free survival: Time to disease recurrence or death as a first event. An analysis plan based on the method of Woolson (1981) will be used to monitor outcome for these patients.
  
  
• Estimated Percentage of Patients With Low-risk Rhabdomyosarcoma Treated With Regimen 2 Therapy Failure Free at 5 Years (95% Confidence Interval). [ Time Frame: 5 years from study enrollment ]
  Failure free survival: Time to disease recurrence or death as a first event. An analysis plan based on the method of Woolson (1981) will be used to monitor outcome for these patients.
  
  

• Rate of Local Failure for Patients Who Receive Reduced Doses of Radiation Therapy [ Time Frame: Up to 10 years ]
  The local failure rate will be estimated using cumulative incidence curves.
  
  
• Rate of Second-look Surgery and the Proportion of Patients Who Are Tumor-free or With Microscopic Tumor Only Following Second-look Surgeries [ Time Frame: At 13 weeks ]
  The decision to perform second-look surgery should be based on the physical examination and imaging studies at Week 12 and should only be considered if a reasonable functional and cosmetic result is anticipated.
  
  
• Rate of Local Failure for Patients With Clinical Group III Disease When the Radiotherapy Dose is Reduced After Second-look Surgical Resection. [ Time Frame: Up to 20 weeks ]
  The local failure rate will be estimated using cumulative incidence curves.
  
  

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.