Clinical trial NCT00354835
Conditions: Adult Rhabdomyosarcoma Childhood Alveolar Rhabdomyosarcoma Childhood Botryoid-Type Embryonal Rhabdomyosarcoma Childhood Embryonal Rhabdomyosarcoma Localized Childhood Soft Tissue Sarcoma Rhabdomyosarcoma Sarcoma Stage I Adult Soft Tissue Sarcoma AJCC v7 Stage II Adult Soft Tissue Sarcoma AJCC v7 Stage III Adult Soft Tissue Sarcoma AJCC v7
Sponsor: Children's Oncology Group
Start date: 2006-12-26; Completion date: 2022-12-31
Enrollment: 481 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with radiation therapy in treating patients with rhabdomyosarcoma.

Detailed description:
PRIMARY OBJECTIVES:

I. To compare the early response rates, failure-free survival (FFS), and survival of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with surgery, radiotherapy, and vincristine (vincristine sulfate), dactinomycin and cyclophosphamide (VAC) or VAC alternating with vincristine, irinotecan (irinotecan hydrochloride) (VI).

SECONDARY OBJECTIVES:

I. To 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 Intergroup Rhabdomyosarcoma Study (IRS)-IV for historic comparison.

II. To compare the acute and late effects of VAC to VAC alternating with VI, including the toxicity associated with concurrent VI and radiotherapy.

III. To compare the acute and late effects of VAC as delivered on this study to D9803 VAC.

IV. To correlate change in fludeoxyglucose F-18 positron emission tomography (FDG-PET) maximum standard uptake value (SUVmax) from week 1 to week 4 and 15 with FFS.

V. For VI treated patients, to correlate patient UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype with VI toxicity. VI. To correlate cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), and glutathione S-transferase alpha 1 (GSTA1) genotypes with VAC toxicity.

VII. To prospectively evaluate and validate gene expression values with the intent to define the best diagnostic predictors and more powerful prognostic classifiers.

VIII. To assess the frequency of bladder dysfunction in patients with bladder, prostate, and pelvic sites of RMS 3-6 years after study enrollment.

OUTLINE: 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 sulfate 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 sulfate 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 up every 2-4 months for 4 years and then annually for 5-10 years.

Arms: arm 1: 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. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. arm 2: 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 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
Interventions: intervention 1: Cyclophosphamide intervention 2: Dactinomycin intervention 3: Irinotecan Hydrochloride intervention 4: Laboratory Biomarker Analysis intervention 5: Questionnaire Administration intervention 6: Radiation Therapy intervention 7: Vincristine Sulfate
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Correlative studies intervention 5: Ancillary studies intervention 6: Undergo radiotherapy intervention 7: Given IV

Protocol documents: