Overview

This trial is active, not recruiting.

Conditions adult rhabdomyosarcoma, embryonal childhood rhabdomyosarcoma, embryonal-botryoid childhood rhabdomyosarcoma, previously untreated childhood rhabdomyosarcoma
Treatments conventional surgery, dactinomycin, cyclophosphamide, vincristine sulfate, radiation therapy
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date September 2004
End date September 2012
Trial size 390 participants
Trial identifier NCT00075582, ARST0331, CDR0000347078, COG-ARST0331, NCI-2009-00425, U10CA098543

Summary

This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine, dactinomycin, and cyclophosphamide, 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. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective in treating low-risk rhabdomyosarcoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive VAC chemotherapy comprising vincristine sulfate 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 sulfate 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 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)
dactinomycin ACT-D
Given IV
cyclophosphamide CPM
Given IV
vincristine sulfate leurocristine sulfate
Given IV
radiation therapy irradiation
Undergo radiotherapy
(Experimental)
Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate 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 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).
conventional surgery surgery, conventional
Some patients may undergo second-look surgery
dactinomycin ACT-D
Given IV
cyclophosphamide CPM
Given IV
vincristine sulfate leurocristine sulfate
Given IV
radiation therapy irradiation
Undergo radiotherapy

Primary Outcomes

Measure
Estimated Percentage of Patients Failure Free at 5 Years (95% Confidence Interval)
time frame: 5 years from study enrollment
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
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

Secondary Outcomes

Measure
Rate of Local Failure for Patients Who Receive Reduced Doses of Radiation Therapy
time frame: Up to 10 years
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
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

Eligibility Criteria

Male or female participants up to 49 years old.

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

Additional 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
Principal investigator David Walterhouse, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Children's Oncology Group.