Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma

Official Title: “RANDOMISED TRIAL OF ADJUVANT CHEMOTHERAPY WITH HIGH-DOSE DOXORUBICIN, IFOSFAMIDE AND LENOGRASTIM IN HIGH GRADE SOFT TISSUE SARCOMA”

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether giving chemotherapy after surgery is more effective than surgery alone in treating soft tissue sarcoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without chemotherapy in treating patients who have soft tissue sarcoma.

OBJECTIVES: - Compare the local disease control, overall survival, and relapse-free survival in patients with high-grade soft tissue sarcoma treated with adjuvant high-dose doxorubicin and ifosfamide plus filgrastim (G-CSF) vs no adjuvant chemotherapy and G-CSF after definitive surgery. - Compare the toxicity and morbidity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, site of primary tumor (extremity vs trunk, including shoulder, pelvic girdle, head, or neck vs central, including intrathoracic, visceral, uterine, or retroperitoneal), size of primary tumor (less than 5 cm vs 5 cm or greater in largest diameter), postoperative radiotherapy (yes vs no), and isolated limb perfusion therapy (yes vs no).

Some patients undergo isolated limb perfusion therapy with cytotoxics and/or cytokines.

No more than 8 weeks after biopsy or inadequate surgery, patients undergo definitive surgery. Patients with complete resection undergo radiotherapy assessment and then randomization. Patients with incomplete or marginal resection (except for central lesions) undergo re-excision and, in the absence of macroscopic disease, assessment for postoperative radiotherapy followed by randomization. - Randomization: Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive no adjuvant chemotherapy or filgrastim (G-CSF). Beginning within 6 weeks after surgery, eligible patients undergo radiotherapy as outlined below. - Arm II: Beginning within 4 weeks after surgery, patients receive high-dose doxorubicin IV over 20 minutes followed by ifosfamide IV over 24 hours and G-CSF subcutaneously daily beginning 24 hours after completion of ifosfamide infusion and continuing for 10 days. Treatment continues every 3 weeks for 5 courses.

Beginning within 6 weeks after completion of chemotherapy, eligible patients undergo radiotherapy as outlined below. - Radiotherapy: Patients with incomplete or marginal resection undergo radiotherapy 5 days a week for 6-6.6 weeks. Patients with complete microscopic resection undergo radiotherapy 5 days a week for 5 weeks followed by boost radiotherapy 5 days a week for 1 week.

Patients are followed every 2 months for 1 year, every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 3.5 years.

Intervention(s) in this Clinical Trial

• Biological: filgrastim
• Drug: doxorubicin hydrochloride
• Drug: ifosfamide
• Drug: isolated perfusion
• Procedure: adjuvant therapy
• Procedure: conventional surgery
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically proven soft tissue sarcoma that is amenable to definitive surgery no more than 8 weeks after biopsy or inadequate surgery
• Eligible subtypes:
• Alveolar soft part sarcoma
• Angiosarcoma
• Fibrosarcoma
• Leiomyosarcoma
• Malignant fibrous histiocytoma
• Liposarcoma (round cell and pleomorphic)
• Miscellaneous sarcoma (including pelvic mixed mesodermal tumors)
• Malignant paraganglioma
• Neurogenic sarcoma
• Rhabdomyosarcoma
• Synovial sarcoma
• Unclassifiable sarcoma
• Ineligible subtypes:
• Chondrosarcoma
• Dermatofibrosarcoma
• Embryonal rhabdomyosarcoma
• Ewing's sarcoma
• Kaposi's sarcoma
• Liposarcoma (myxoid and well differentiated)
• Malignant mesothelioma
• Neuroblastoma
• Osteosarcoma
• Confirmed high-grade tumor (i.e., Trojani Grade II or III)
• No metastases on staging with chest x-ray and thoracic CT scan
• No regional lymph node involvement
• Locally recurrent disease allowed
• Interval of 3 months or more between definitive surgery and recurrence

PATIENT CHARACTERISTICS:

Age:

• 16 to 69

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm^3
• Platelet count greater than 120,000/mm^3
• No bleeding disorders

Hepatic:

• Bilirubin no greater than 1.25 times normal
• No severe hepatic dysfunction

Renal:

• Creatinine less than 1.6 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No clear history of angina
• No documented myocardial infarction
• No existing cardiac failure

Other:

• No serious infection
• No other malignancy except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to affected area

Surgery:

• See Disease Characteristics

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 69 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: European Organization for Research and Treatment of Cancer - EORTC Other

Overall Clinical Trial Officials and Contacts

Penella J. Woll, MD, PhD Study Chair Cancer Research Centre at Weston Park Hospital  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002641

Study ID Number: CDR0000064132

ClinicalTrials.gov Identifier: NCT00002641

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database