Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as doxorubicin and ifosfamide use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors, such as pegfilgrastim, cause the body to make blood cells. It is not yet known whether doxorubicin alone is more effective with or without ifosfamide and pegfilgrastim in treating soft tissue sarcoma. PURPOSE: This randomized phase III trial is studying giving doxorubicin alone to see how well it works compared to giving doxorubicin together with ifosfamide and pegfilgrastim in treating patients with locally advanced or metastatic soft tissue sarcoma.

Detailed Description
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OBJECTIVES: Compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin with vs without ifosfamide and pegfilgrastim as first-line therapy. Compare the response in patients treated with these regimens. Compare the treatment-related mortality of patients treated with these regimens. Compare the toxicity of these regimens in these patients. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to WHO performance status (0 vs 1), age group (less than 50 years of age vs 50 years of age and over), presence of liver metastases (yes vs no), histological grade (2 vs 3), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive doxorubicin IV on day 1 (or IV continuously on days 1-3). Arm II: Patients receive doxorubicin IV on days 1-3 and ifosfamide IV over 4 hours on days 1-4. Patients also receive pegfilgrastim subcutaneously on day 5. In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 4 years.

Official Title
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Randomised Trial Of Single Agent Doxorubicin Versus Doxorubicin Plus Ifosfamide In The First Line Treatment Of Advanced Or Metastatic Soft Tissue Sarcoma

Conditions
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Sarcoma

Intervention / Treatment
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* Biological: pegfilgrastim
* Drug: doxorubicin hydrochloride
* Drug: ifosfamide
* Procedure: multimodality therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed soft tissue sarcoma Locally advanced unresectable* OR metastatic disease High-grade (grade 2-3) disease according to the FNLCC grading system NOTE: *Disease that could prove resectable (including pulmonary metastasectomy) after a response to chemotherapy is allowed The following tumor types are eligible: Malignant fibrous histiocytoma Myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma Pleomorphic rhabdomyosarcoma Synovial sarcoma Myxofibrosarcoma, intermediate and high-grade Fibrosarcoma Leiomyosarcoma Angiosarcoma Malignant peripheral nerve sheath tumor Epithelioid sarcoma Alveolar rhabdomyosarcoma Unclassifiable sarcoma, not otherwise specified The following tumor types are not eligible: Gastrointestinal stromal tumor Mixed mesodermal tumor Chondrosarcoma Malignant mesothelioma Neuroblastoma Osteosarcoma Ewing's sarcoma/primitive neuroectodermal tumor Desmoplastic small round cell tumor Embryonal rhabdomyosarcoma Alveolar soft part sarcoma Must have a measurable lesion with clinical evidence of progression within the past 6 weeks Osseous lesions and pleural effusions are not considered measurable No known or symptomatic CNS metastases PATIENT CHARACTERISTICS: Age 18 to 60 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.8 mg/dL Albumin at least 2.5 g/dL Renal Creatinine no greater than 1.4 mg/dL OR Creatinine clearance greater than 65 mL/min Cardiovascular No history of cardiovascular disease Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception No other severe medical illness No psychosis No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix or basal cell skin cancer No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up schedule PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for advanced or metastatic disease Prior adjuvant chemotherapy allowed provided there was no disease progression within 6 months after completion of treatment Endocrine therapy Not specified Radiotherapy No prior radiotherapy to the sole index lesion Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: pegfilgrastim|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: ifosfamide|nan|
|Procedure: multimodality therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response as assessed by RECIST criteria |  |  | 
| Toxicity as assessed by CTC 2.0 |  |  | 
| Treatment-related mortality |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult angiosarcoma, adult epithelioid sarcoma, adult fibrosarcoma, adult leiomyosarcoma, adult liposarcoma, adult rhabdomyosarcoma, adult synovial sarcoma, stage III adult soft tissue sarcoma, adult malignant fibrous histiocytoma, adult neurofibrosarcoma, stage II adult soft tissue sarcoma, stage IV adult soft tissue sarcoma