liposomal doxorubicin plus ifosfamide in treating patients with advanced or metastatic soft tissue sarcoma

Conditions: Sarcoma

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells. purpose: phase i trial to study the effectiveness of combining liposomal doxorubicin with ifosfamide in treating patients who have advanced or metastatic soft tissue sarcoma.

objectives: * determine the maximum tolerated dose of ifosfamide in combination with doxorubicin hcl liposome in patients with previously untreated advanced or metastatic soft tissue sarcoma. * determine the objective response in patients treated with this regimen. * determine the dose-limiting toxicity in patients treated with this regimen. outline: this is a multicenter, dose-escalation study of ifosfamide. patients receive doxorubicin hcl liposome iv over 1 hour on day 1 and ifosfamide iv over 4 hours on days 1-3 or on days 1-4 (for patients enrolled on dose level 6). treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of ifosfamide until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. projected accrual: a total of 3-24 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed soft tissue sarcoma * advanced and/or metastatic disease * must be of any of the following types: * malignant fibrous histiocytoma * liposarcoma (excluding lipomas and well-differentiated liposarcomas) * rhabdomyosarcoma * synovial sarcoma * malignant paraganglioma * fibrosarcoma * leiomyosarcoma * angiosarcoma * neurogenic sarcoma * sarcoma not otherwise specified * paraffin blocks and slides must be available * measurable disease * osseous lesions and pleural effusions are not considered measurable disease * evidence of progressive disease within the past 6 weeks * the following conditions are excluded: * gastrointestinal stromal tumors * malignant mesothelioma * chondrosarcoma * neuroblastoma * osteosarcoma * ewing's sarcoma * embryonal rhabdomyosarcoma * no symptomatic or known cns metastases patient characteristics: age: * 18 to 70 performance status: * who 0-1 life expectancy: * not specified hematopoietic: * wbc at least 4,000/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.75 mg/dl * albumin at least 2.5 g/dl renal: * creatinine no greater than 1.4 mg/dl * creatinine clearance at least 65 ml/min cardiovascular: * ejection fraction at least 50% by echocardiogram or isotopic methods * no history of cardiovascular disease other: * no other prior or concurrent primary malignancies except adequately treated carcinoma in situ of the cervix or basal cell carcinoma * no other severe medical illness * no psychosis * no psychological, familial, sociological, or geographical condition that would preclude study participation * not pregnant * fertile patients must use effective contraception (barrier method for men) during and for 6 months after study participation prior concurrent therapy: biologic therapy: * not specified chemotherapy: * no prior chemotherapy for advanced disease * no other concurrent systemic chemotherapy for malignancy endocrine therapy: * not specified radiotherapy: * no prior radiotherapy to sole indicator lesion * concurrent radiotherapy allowed except to sole indicator lesion surgery: * not specified other: * no other concurrent investigational drugs

Keywords: adult angiosarcoma adult fibrosarcoma adult leiomyosarcoma adult liposarcoma adult neurofibrosarcoma adult synovial sarcoma stage iii adult soft tissue sarcoma adult alveolar soft-part sarcoma adult epithelioid sarcoma adult malignant fibrous histiocytoma adult malignant hemangiopericytoma adult malignant mesenchymoma adult rhabdomyosarcoma stage iv adult soft tissue sarcoma