sorafenib in treating patients with angiosarcoma that is locally advanced, metastatic, or unable to be removed by surgery

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 angiosarcoma that is locally advanced, metastatic, or unable to be removed by surgery.

objectives: primary * determine the rate of non-progression at 9 months in patients with unresectable, locally advanced, or metastatic angiosarcoma treated with sorafenib tosylate. secondary * determine the rate of non-progression at 60, 120, and 180 days. * determine the median time to progression. * determine overall survival. * determine the best response rate. * determine the clinical and biological factors that predict clinical benefit. * evaluate tolerability by nci ctcae v3.0. * correlate efficacy with plasma expression of genes implicated in controlling angiogenesis. * explore the tumor expression of these genes in tissue from a tumor bank. outline: this is a multicenter study. patients are stratified according to disease type (cutaneous angiosarcoma \[scalp, breast, or soft tissue\] vs visceral angiosarcoma). all patients receive oral sorafenib tosylate twice daily for 9 months in the absence of disease progression or unacceptable toxicity.

Eligibility criteria:
disease characteristics: * histologically confirmed angiosarcoma * locally advanced or metastatic disease * unresectable disease * no kaposi sarcoma, hemangiopericytoma, or hemangioendothelioma * measurable tumor with at least 1 measurable lesion by recist criteria * tumor in a previously irradiated area must not show progression * no brain metastases or meningeal tumors (symptomatic or asymptomatic) patient characteristics: * who performance status 0-2 * life expectancy ≥ 3 months * wbc ≥ 3,000/mm³ * anc ≥ 1,500/mm³ * platelet count ≥ 100,000/mm³ * hemoglobin ≥ 9 g/dl * pt or inr and aptt ≤ 1.5 times upper limit of normal (uln) * anticoagulation treatment with heparin or vitamin k allowed if the above criteria are met * liver transaminases ≤ 2.5 times uln (≤ 5 times uln in the presence of liver metastases) * total bilirubin ≤ 1.5 times uln * serum creatinine ≤ 1.5 times uln * amylase and lipase ≤ 1.5 times uln * not pregnant or nursing * weight loss from pre-disease weight \< 20% over the past 12 months * able to swallow * no active or ischemic coronary artery disease * no myocardial infarction within the past 6 months * no nyha class iii-iv cardiac failure * no uncontrolled hypertension * no coagulopathy * no active uncontrolled peptic ulcer * no patients on renal dialysis * no active bacterial or fungal infection \> ctcae v3.0 grade 2 * no hiv or hepatitis b or c positivity * no chronic unstable illness that could jeopardize patient safety or compliance * no other progressive or malignant tumor * no known or suspected allergy to sorafenib tosylate * no psychological, familial, social, or geographic situations that preclude clinical follow up * no patients deprived of liberty or under guardianship * no cardiac arrhythmia requiring antiarrhythmic medication (except beta-blockers or digoxin for chronic atrial fibrillation) * no epilepsy requiring antiepileptic drugs prior concurrent therapy: * see patient characteristics * no prior organ or peripheral stem cell transplantation * no more than 2 prior lines of chemotherapy * at least 28 days since prior treatment (systemic or major surgery) * no concurrent therapy for another malignancy * no concurrent cyp3a inducers (e.g., rifampicin, st. john wort, phenytoin, carbamazepine, phenobarbital, dexamethasone)

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