ecteinascidin 743 in treating patients with unresectable 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. purpose: phase ii trial to study the effectiveness of ecteinascidin 743 in treating patients who have unresectable advanced or metastatic soft tissue sarcoma.

objectives: i. determine the rate of clinical benefit, in terms of the incidence of objective partial and complete response, stable disease, or minor response of more than 3 months duration, in patients with previously treated, unresectable advanced or metastatic soft tissue sarcoma treated with ecteinascidin 743. ii. determine the progression-free survival, overall survival, and response duration in patients treated with this drug. iii. determine the toxicity profile of this drug in these patients. iv. determine the pharmacokinetic-pharmacodynamic relationship of this drug in these patients. outline: this is a multicenter study. patients are stratified according to number of prior cytotoxic therapies for advanced disease (1-2 vs more than 2). patients receive ecteinascidin 743 iv over 3 hours on day 1. treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. patients are followed every 3 months. projected accrual: a total of 36-76 patients (18-38 per stratum) will be accrued for this study within 13 months.

Eligibility criteria:
disease characteristics: histologically confirmed advanced or metastatic soft tissue sarcoma unresectable disease previously treated with at least 1 prior non-adjuvant chemotherapy regimen for advanced or metastatic disease adjuvant chemotherapy considered first-line treatment for advanced disease if the first relapse is less than 6 months after completion of therapy at least 1 bidimensionally measurable non-irradiated lesion at least 20 mm in at least 1 diameter by ct scan at least 20 by 20 mm for clinically measurable lesion no gastrointestinal stromal sarcoma no hiv-related kaposi's sarcoma no malignant mesothelioma no chondrosarcomas no symptomatic brain or leptomeningeal involvement patient characteristics: age: 18 and over performance status: who 0-2 or karnofsky 60-100% life expectancy: at least 3 months hematopoietic: neutrophil count at least 1,500/mm3 platelet count at least 100,000/mm3 hepatic: bilirubin no greater than upper limit of normal (uln) alkaline phosphatase no greater than uln (unless suspected bone metastases present) ast/alt less than 2.5 times uln albumin at least 2.5 g/dl no chronic active liver disease renal: creatinine no greater than 1.8 mg/dl or creatinine clearance at least 40 ml/min cardiovascular: no congestive heart failure no angina pectoris, even if medically controlled no myocardial infarction within the past year no uncontrolled arterial hypertension or arrhythmias other: no other neoplastic disease within the past 5 years except non-melanoma skin cancer or carcinoma in situ no other serious illness or medical condition no active infection no history of significant neurological or psychiatric disorders no symptomatic peripheral neuropathy grade 2 or greater not pregnant or nursing negative pregnancy test fertile patients must use effective contraception during and for 1 month after study prior concurrent therapy: biologic therapy: recovered from prior immunotherapy no concurrent prophylactic colony-stimulating factors (e.g., filgrastim (g- csf) or sargramostim (gm-csf)) during first course of study no concurrent anticancer immunotherapy chemotherapy: see disease characteristics at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered no other concurrent chemotherapy endocrine therapy: no concurrent anticancer hormonal therapy radiotherapy: see disease characteristics recovered from radiotherapy no concurrent radiotherapy except palliative local radiotherapy surgery: see disease characteristics other: at least 30 days since prior investigational drugs no other concurrent investigational or experimental anticancer drugs no concurrent participation in other clinical trial

Keywords: stage iii adult soft tissue sarcoma recurrent adult soft tissue sarcoma stage iv adult soft tissue sarcoma