Overview

This trial is active, not recruiting.

Condition sarcoma
Treatments dactinomycin, cyclophosphamide, doxorubicin hydrochloride, etoposide, ifosfamide, irinotecan hydrochloride, vincristine sulfate, conventional surgery, radiation therapy, filgrastim
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date July 2006
End date January 2010
Trial size 109 participants
Trial identifier NCT00354744, ARST0431, CDR0000489215, COG-ARST0431

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
dactinomycin Actinomycin-D
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
cyclophosphamide Cytoxan
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
doxorubicin hydrochloride Adriamycin
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
etoposide VePesid
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
ifosfamide Isophosphamide
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
irinotecan hydrochloride CPT-11
Dosage 50 mg/m2-max dose 100 mg/day. Days 1-5 of weeks 1, 4, 20, 23, 47 and 50. Given IV
vincristine sulfate Oncovin
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
conventional surgery
Resection of the primary tumor with a surrounding "envelope" of normal tissue
radiation therapy
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
filgrastim Granulocyte Colony-Stimulating Factor
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.

Primary Outcomes

Measure
Tumor Response Rate
time frame: Protocol week 6 evaluation
Estimate of the Percent of Patients Event Free at 4 Years Following Study Entry
time frame: 4 years

Secondary Outcomes

Measure
Early Disease Control
time frame: 2 years
Feasibility
time frame: 2 years
Toxicity
time frame: 2 years

Eligibility Criteria

Male or female participants up to 49 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed high-risk rhabdomyosarcoma or ectomesenchymoma - Prior enrollment on COG-D9902 to confirm local histological diagnosis required - Tissue must be submitted for pathologic review within 2 days of patient registration on COG-D9902 - Newly diagnosed disease - Metastatic disease (stage IV, clinical group IV) - Has undergone initial surgical procedure (including biopsy) that provided the definitive diagnosis within the past 42 days - Parameningeal and paraspinal tumors allowed - Patients with parameningeal (without intracranial extension [ICE]) and paraspinal tumors should begin study chemotherapy at week 1 and radiotherapy at week 20 - Patients with evidence of ICE, as defined by contrast MRI showing that primary tumor touches, displaces, invades, distorts, or otherwise causes a signal abnormality of the dura in contiguity to the primary site in brain or spinal cord, are eligible - ICE is presumed to exist if the cerebrospinal fluid cytopathology is positive for tumor at diagnosis - Patients requiring emergency radiotherapy are eligible - Patients requiring emergency radiotherapy (for intracranial extension or spinal cord impingement) should begin study chemotherapy at week 1 (irinotecan hydrochloride and vincristine) concurrently with radiation therapy PATIENT CHARACTERISTICS: - ECOG or Zubrod performance status (PS) 0-2 (Lansky PS 50-100% for patients < 10 years of age and Karnofsky PS 50-100% for patients ≥ 10 years of age) - Absolute neutrophil count ≥ 750/mm³* - Platelet count ≥ 75,000/mm³* - Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min (≥ 40 mL/min for infants < 1 year of age) - Patients with urinary tract obstruction by tumor must meet the renal function criteria listed above AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract - SGPT < 2.5 times normal - Bilirubin < 1.5 mg/dL - Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by MUGA - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during study and for ≥ 1 month after study completion - No evidence of uncontrolled infection - Able to undergo radiotherapy NOTE: *Abnormal blood counts allowed if there is bone marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma PRIOR CONCURRENT THERAPY: - No prior chemotherapy except steroids - No prior radiotherapy - No concurrent aprepitant during ifosfamide or doxorubicin hydrochloride chemotherapy - No concurrent dexrazoxane - No concurrent sargramostim (GM-CSF) or pegfilgrastim

Additional Information

Official title Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma
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 of concurrent irinotecan hydrochloride and radiotherapy in these patients. - 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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2013.
Information provided to ClinicalTrials.gov by Children's Oncology Group.