Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

Children's Oncology Group

Status and phase: Completed; Phase 3

Conditions: Sarcoma

Treatments: Biological: dactinomycin; Biological: sargramostim; Drug: vincristine sulfate; Drug: cyclophosphamide; Radiation: radiation therapy; Biological: filgrastim

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00002995

D9602

IRS-D9602 (Other Identifier)

CDR0000065542 (Other Identifier)

CCG-D9602 (Other Identifier)

POG-D9602 (Other Identifier)

COG-D9602 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether chemotherapy is more effective with or without radiation therapy in treating patients who have rhabdomyosarcoma.

PURPOSE: Phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy in treating patients who have newly-diagnosed rhabdomyosarcoma.

Full description

OBJECTIVES:

• Determine the failure-free survival (FFS) rate in patients with newly diagnosed low-risk rhabdomyosarcoma of embryonal or botryoid subtype meeting criteria for group I after treatment with dactinomycin and vincristine with or without radiotherapy.
• Determine the FFS rate in these patients meeting criteria for group II after treatment with dactinomycin, vincristine, and cyclophosphamide with or without radiotherapy.
• Determine the FFS rate in patients with ectomesenchymomas containing rhabdomyosarcomatous elements (embryonal histiotype) who receive one of the above treatments.
• Determine new molecular markers specific to embryonal and botryoid tumor histologies which are of diagnostic and prognostic significance in patients treated with these regimens.

OUTLINE: Patients are assigned to 1 of 2 groups, depending on histology and site of disease.

• Group I (favorable tumor site, negative lymph nodes, stage 1, clinical group I, IIA, or III (orbit only), node negative [N0] OR unfavorable tumor site, negative or unknown lymph nodes, stage 2, clinical group I): Patients receive vincristine IV over 1 minute weekly for 8 weeks and dactinomycin IV over 1 minute once every 3 weeks for 4 doses. Treatment repeats every 12 weeks for 4 courses. Radiotherapy is administered to patients with clinical group II or III disease on weeks 3-8.
• Group II (favorable tumor site, positive lymph nodes, stage 1, clinical group III (orbit only), node positive [N1] OR favorable tumor site except orbit, any lymph nodes, stage 1, clinical group III OR unfavorable tumor site, stage 2, clinical group II OR unfavorable tumor site, stage 3, clinical group I or II): Patients receive vincristine and dactinomycin as in group I. Patients also receive cyclophosphamide IV over 30-60 minutes and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously once daily beginning 24 hours after completion of chemotherapy and continuing for 10 days or until blood counts recover. Radiotherapy is administered on weeks 3-8, 12-17, or 28-33, if clinically indicated as in group I.

Patients are followed every 3-4 months for 3 years (4 years after diagnosis), every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 254 patients for group I will be accrued for this study within 6 years. Approximately 12 patients per year will be accrued for group II.

Enrollment: 483 patients

Sex: All

Ages: Under 49 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed embryonal (EMB) rhabdomyosarcoma (RMS) or botryoid or spindle cell variants of EMB RMS or embryonal ectomesenchymoma meeting 1 of the following criteria:

  • Stage 1, no clinical group IV: Tumor in favorable site (orbit, head and neck [excluding parameningeal], genitourinary [not bladder/prostate], or biliary tract) and no metastatic disease
  • Stage 2 or 3, clinical group I or II: Tumor in unfavorable site (bladder/prostate, extremity, cranial parameningeal, trunk, retroperitoneum, pelvis, perineal/perianal, intrathoracic, gastrointestinal, or liver), no gross residual disease after initial surgery, and no metastatic disease

• Must have ipsilateral lymph node dissection if age 10 or over with primary paratesticular cancer OR under age 10 with clinically positive regional lymph nodes

• Low risk of recurrence

• Previously untreated disease

• No alveolar RMS or undifferentiated sarcoma

• No intermediate-risk disease

• No metastatic disease at diagnosis

PATIENT CHARACTERISTICS:

Age:

• Under 50

Performance status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin elevation secondary to biliary or hepatic primaries allowed

Renal:

• Creatinine elevation secondary to tumor obstruction allowed

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified