Title
Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma
Randomized Study Comparing Neoadjuvant Chemotherapy Etoposide + Ifosfamide + Adriamycin (EIA) Combined With Regional Hyperthermia (RHT) Versus Neoadjuvant Chemotherapy Alone in the Treatment of High-Risk Soft Tissue Sarcomas in Adults
Phase
Phase 3Study Type
InterventionalStatus
Completed No Results PostedIndication/Condition
SarcomaIntervention/Treatment
doxorubicin ifosfamide etoposide ...Study Participants
340RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. It is not known whether receiving chemotherapy plus hyperthermia is more effective than receiving chemotherapy alone in treating patients with soft tissue sarcoma.
PURPOSE: This randomized phase III trial is studying combination chemotherapy alone to see how well it works compared to combination chemotherapy and hyperthermia therapy in treating patients with soft tissue sarcoma.
OBJECTIVES:
Determine local progression-free survival of patients with high-risk soft tissue sarcoma treated with neoadjuvant etoposide, ifosfamide, and doxorubicin with or without regional hyperthermia.
Determine the tumor response rate, local disease control rate, and overall survival in patients treated with this regimen.
OUTLINE: This is a randomized study. Patients are stratified according to high-risk category (S1 vs S2 vs S3) and disease site (extremity vs nonextremity). Patients are randomized to one of two treatment arms.
Arm I: Patients receive etoposide IV over 30 minutes on days 1 and 4, ifosfamide IV over 60 minutes on days 1-4, and doxorubicin IV over 30 minutes on day 1. Treatment continues every 21 days for a total of 4 courses. Patients also undergo regional hyperthermia.
Arm II: Patients receive chemotherapy alone as in arm I. Patients in both arms undergo definitive surgery 4-6 weeks after chemotherapy. Patients also undergo radiotherapy beginning 4-6 weeks after surgery. After completion of surgery and radiotherapy, patients with non-resectable tumors showing no disease progression receive an additional 4 courses of chemotherapy with or without regional hyperthermia according to above treatment schedule.
Patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 340 patients (170 patients per arm) will be accrued for this study within 3.5 years.
DISEASE CHARACTERISTICS: Histologically proven grade II or III soft tissue sarcoma of one of following high-risk groups: Grade II/III primary tumor with lesion size of at least 5 cm, deep, and extracompartmental (S1) Local recurrence of primary tumor (S2) Inadequate surgical excision of S1 or S2 (S3) Disease recurrence after prior surgery allowed The following histological types are eligible: Malignant fibrous histiocytoma Liposarcoma (round cell and pleomorphic) Leiomyosarcoma Fibrosarcoma Rhabdomyosarcoma Synovial sarcoma Malignant paraganglioma Neurofibrosarcoma (malignant schwannoma) Extraskeletal Ewing's sarcoma Extraskeletal osteosarcoma Malignant peripheral neuroectodermal tumors Mesenchymal chondrosarcoma Angiosarcoma Miscellaneous sarcoma Unclassified sarcoma No distant metastases PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: WHO 0-2 OR Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 No bleeding disorder Hepatic: Bilirubin less than 1.25 times upper limit of normal No severe hepatic dysfunction Renal: Creatinine clearance greater than 60 mL/min No chronic renal failure Cardiovascular: No documented existing cardiac failure No manifest heart failure (New York Heart Association class III or IV) Left ventricular ejection fraction no more than 10% below institutional normal Other: No other prior or concurrent malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix No other severe disease No severe cerebrovascular disease No extremely obese patients No prior metallic implants relevant to the regional hyperthermia field Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy (except to disease recurrence outside study irradiation field) Surgery: See Disease Characteristics No prior mutilative surgery
