Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. Determine the failure-free survival of patients with newly diagnosed low-risk rhabdomyosarcoma treated with vincristine, dactinomycin, cyclophosphamide, and radiotherapy.

Secondary

1. Determine local control rates in patients treated with this regimen.
2. 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.
3. Determine the local control rates in patients with clinical group III disease treated with response-adjusted radiotherapy doses after second-look surgical resection.

Entry Criteria

Disease Characteristics:

• 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:
    • 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

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

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

Endocrine therapy

• Prior steroids allowed

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics

Patient Characteristics:

Age

• Under 50
  • No infants who would not be able to receive study radiotherapy, in the opinion of the treating physician

Performance status

• ECOG 0-2

  OR

• Karnofsky 50-100% (≥ 16 years old)

  OR

• Lansky 50-100% (< 16 years old)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 750/mm³
• Platelet count at least 75,000/mm³ (transfusion independent)

Hepatic

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

 [Note: *Patients with primary hepatic or biliary tumors and bilirubin greater than 1.5 times ULN allowed provided all other eligibility criteria are met]

Renal

• 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

  OR

• Creatinine clearance* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m²

 [Note: *Patients with tumors obstructing the urinary tract causing elevated creatinine allowed provided all other eligibility criteria are met and unimpeded urinary flow is established via decompression of the obstructed portion of the urinary tract]

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection

Expected Enrollment

A total of 510 patients (410 for regimen I [subset 1] and 100 for regimen II [subset 2]) will be accrued for this study within 6 years. ((Subset 1 closed to accrual as of 08/13/2010)

Outcomes

Failure-free survival

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): 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, administered as in regimen I, and continued VA* chemotherapy as in regimen I or II.

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

Walterhouse DO, Meza JL, Breneman JC, et al.: Local control and outcome in children with localized vaginal rhabdomyosarcoma: a report from the Soft Tissue Sarcoma committee of the Children's Oncology Group. Pediatr Blood Cancer 57 (1): 76-83, 2011.[PUBMED Abstract]

Chang HL, Rosenberg AE, Friedmann AM, et al.: Primary pulmonary rhabdomyosarcoma in a 5-month-old boy: a case report. J Pediatr Hematol Oncol 30 (6): 461-3, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

David Walterhouse, MD, Protocol chair		Ph: 773-775-6514
Alberto Pappo, MD, Protocol co-chair(Contact information may not be current)		Ph: 832-822-4200

Related Information

PDQ® clinical trial COG-D9902

Registry Information
Official Title		Vincristine, Dactinomycin, And Lower Doses Of Cyclophosphamide With or Without Radiation Therapy For Patients With Newly Diagnosed Low-Risk Embryonal/Botryoid/Spindle Cell Rhabdomyosarcoma
Trial Start Date		2004-09-20
Trial Completion Date		2010-08-20 (estimated)
Registered in ClinicalTrials.gov		NCT00075582
Date Submitted to PDQ		2003-11-20
Information Last Verified		2011-09-14
NCI Grant/Contract Number		CA98543

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