s0505 sorafenib in treating patients with advanced soft tissue sarcomas

Conditions: Sarcoma

Summary: rationale: sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. purpose: this phase ii trial is studying how well sorafenib works in treating patients with advanced soft tissue sarcomas.

objectives: * determine the objective response rate (confirmed, complete, and partial) in patients with advanced soft tissue sarcomas treated with sorafenib. * determine the 4-month progression-free survival rate in patients treated with this drug. * determine the frequency and severity of adverse events in patients treated with this drug. other objectives (if funding permits): * correlate, preliminarily, a decrease in standard uptake variable (suv) of target lesions by positron-emission tomography scan at 4 weeks with response in patients treated with this drug. * correlate, preliminarily, the phosphorylation status of kit, pdgfr, vegfr, and the raf/mek/erk pathway with response in patients treated with this drug. * correlate, preliminarily, the most common b-raf kinase mutation with response in patients treated with this drug. outline: this is a multicenter study. patients are stratified according to histology (leiomyosarcoma vs liposarcoma vs angiosarcoma, hemangiosarcoma, or hemangiopericytoma). patients receive oral sorafenib twice daily on days 1-28. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed every 8 weeks until disease progression and then every 6 months for 2 years and annually for up to 3 years. projected accrual: a total of 45-75 patients (15-25 per stratum) will be accrued for this study within 15-38 months.

Eligibility criteria:
disease characteristics: * histologically confirmed soft tissue sarcoma of 1 of the following histologies: * angiosarcoma, cutaneous or visceral * malignant hemangiosarcoma * malignant hemangiopericytoma * grade 3-4 leiomyosarcoma * grade 3-4 liposarcoma * must have evidence of unresectable residual disease, metastatic disease, or recurrent disease by radiography * measurable disease by x-ray, scans, or physical examination * archived paraffin-embedded tumor sections available * no known brain metastases patient characteristics: age * 18 and over performance status * zubrod 0-1 life expectancy * not specified hematopoietic * wbc ≥ 3,000/mm\^3 * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 hepatic * sgot and sgpt ≤ 2.5 times upper limit of normal (uln) (5 times uln if due to liver metastases) * bilirubin normal (≤ 2.5 times uln if due to liver metastases) * pt, ptt, and inr normal renal * creatinine normal or * creatinine clearance ≥ 60 ml/min cardiovascular * no history of thromboembolic disease * no uncontrolled hypertension other * not pregnant or nursing * fertile patients must use effective contraception * able to swallow oral medication * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage i or ii cancer in complete remission prior concurrent therapy: biologic therapy * not specified chemotherapy * at least 28 days since prior chemotherapy (42 days for carmustine or mitomycin) and recovered * prior adjuvant chemotherapy allowed * no more than 1 prior chemotherapy regimen for metastatic disease endocrine therapy * not specified radiotherapy * at least 28 days since prior radiotherapy and recovered * must have evidence of disease progression within, or measurable disease outside of, the radiation field after completion of radiotherapy surgery * at least 28 days since prior major surgery and recovered other * no prior sorafenib * no prior inhibitor of vegfr or mapk pathway * no concurrent combination antiretroviral therapy for hiv-positive patients * no other concurrent investigational agents * no concurrent therapeutic anticoagulation * no concurrent administration of any of the following medications: * rifampin * hypericum perforatum (st. john's wort) * cytochrome p450 enzyme-inducing antiepileptic drugs, including any of the following: * phenytoin * carbamazepine * phenobarbital

Keywords: adult angiosarcoma adult leiomyosarcoma adult liposarcoma adult malignant hemangiopericytoma recurrent adult soft tissue sarcoma stage iii adult soft tissue sarcoma stage iv adult soft tissue sarcoma