Sorafenib 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.

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)