Clinical trial NCT00354744
Conditions: Sarcoma
Keywords: adult rhabdomyosarcoma previously untreated childhood rhabdomyosarcoma adult malignant mesenchymoma childhood malignant mesenchymoma metastatic childhood soft tissue sarcoma stage IV adult soft tissue sarcoma
Sponsor: Children's Oncology Group
Start date: 2006-07-01; Completion date: 2019-06-30
Enrollment: 109 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as vincristine, irinotecan, ifosfamide, etoposide, doxorubicin, cyclophosphamide, and dactinomycin, 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 high-dose combination chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase III trial is studying how well giving high-dose combination chemotherapy together with radiation therapy works in treating patients with newly diagnosed metastatic rhabdomyosarcoma or ectomesenchymoma.

Detailed description:
OBJECTIVES:

Primary

* Improve the early disease control interval for patients with newly diagnosed, high-risk, metastatic rhabdomyosarcoma or ectomesenchymoma using intensive, interval-compression therapy (comprising vincristine, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin) that permits maximal early exposure to known effective agents.
* Determine the feasibility and assess immediate- and short-term side effects of concurrent irinotecan hydrochloride and radiotherapy in these patients.

Secondary

* Expand the available data for response to irinotecan hydrochloride and vincristine in previously untreated patients with high-risk rhabdomyosarcoma.
* Evaluate, prospectively, and validate gene expression values with the intent to define the best diagnostic predictors and more powerful prognostic classifiers.

OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are stratified according to prognostic factors predictive of outcome (e.g. histology, bone/bone marrow involvement, and number of metastatic sites).

Patients receive high-dose chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; and ifosfamide IV over 1 hour and etoposide IV over 30-60 minutes on days 1-5 of weeks 9, 13, 17, 26, and 30. Patients also receive doxorubicin hydrochloride IV continuously over 24 hours on days 1 and 2 of weeks 7\*, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; and dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44 in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously in weeks 7-9, 11-13, 15-17, 22, 26, 28-30, 32, 33, 35, 38, and 41-44 beginning 24-36 hours after the last chemotherapy dose and continuing until blood counts recover.

NOTE: \*Patients undergoing early radiotherapy for intracranial extension do not receive doxorubicin in week 7.

Beginning at week 20 (or week 1 for patients with parameningeal tumors with intracranial extension \[or spinal cord compression\] requiring emergency radiotherapy), patients also undergo radiotherapy once a day, 5 days a week, for approximately 5½ weeks. Some patients may also undergo second-look surgery.

After completion of study treatment, patients are followed periodically for ≥ 10 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Arms: arm 1: Parameningeal (without intracranial extension) and paraspinal tumors receive chemotherapy starting Week 1 and begin radiation therapy at Week 20. Weeks 1-6: vincristine sulfate and irinotecan hydrochloride. Weeks 7-34: vincristine sulfate and irinotecan hydrochloride, Cyclophosphamide with MESNA, Doxorubicin hydrochloride, Etoposide, Ifosfamide with MESNA. Weeks 35-54: vincristine sulfate, Dactinomycin, irinotecan hydrochloride and Cyclophosphamide with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients.
Interventions: intervention 1: dactinomycin intervention 2: cyclophosphamide intervention 3: doxorubicin hydrochloride intervention 4: etoposide intervention 5: ifosfamide intervention 6: irinotecan hydrochloride intervention 7: vincristine sulfate intervention 8: conventional surgery intervention 9: radiation therapy intervention 10: filgrastim
Intervention descriptions: intervention 1: Age based dosage: ≥ 1 year 0.045 mg/kg IV x 1(maximum dose 2.5 mg), \< 1 year 0.025 mg/kg.

Day 1 of Weeks 35, 38, 41 and 44.

Given IV intervention 2: Age based dosage: ≥ 3 years 1200 mg/m2, \<3 years 40 mg/kg.

Day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41 and 44.

Given IV intervention 3: Age based dosage: ≥ 1 year: 37.5mg/m²/day, \< 1 year: treat with 50% doses calculated on a m2 basis. Total dose 75 mg/m².

Days 1 and 2 of weeks 7, 11, 15, 28 and 32.

Given IV intervention 4: Age based dosage: ≥ 1 year: 100 mg/m²/day, \< 1 year: treat with 50% doses calculated on a m2 basis.

Days 1-5 of weeks 9, 13, 17, 26 and 30.

Given IV intervention 5: Age based dosage: ≥ 1 year: 1800 mg/m²/day, \< 1 year: treat with 50% doses calculated on a m2 basis.

Days 1-5 of weeks 9, 13, 17, 26 and 30.

Given IV intervention 6: Dosage 50 mg/m2-max dose 100 mg/day.

Days 1-5 of weeks 1, 4, 20, 23, 47 and 50.

Given IV intervention 7: Age based dosage: ≥ 3 years 1.5 mg/m2 (max dose 2 mg), ≥ 1 year and \< 3 years 0.05 mg/kg (max dose 2 mg), \< 1 year 0.025 mg/kg.

Days 1-5 of weeks 1, 2, 3, 4, 5, 7, 8, 11, 12, 15, 16, 20, 21, 22, 23, 24, 28, 29, 32, 33, 35, 38, 41, 42, 43, 44, 47, 48, 50, and 51.

Given IV intervention 8: Resection of the primary tumor with a surrounding "envelope" of normal tissue intervention 9: Radiotherapy beginning at Week 20 to the primary tumor and to the metastatic sites excepting those with parameningeal tumors with intracranial extension (direct extension into the brain) and those requiring emergency radiotherapy intervention 10: 5 micrograms/kg/day (max 300 micrograms) beginning 24-36 hours after the last dose of chemotherapy. Continue at least 7 days, or until the ANC ≥750/μL whichever comes last.

Given subcutaneously.

Protocol documents: