Bevacizumab in Treating Patients With Angiosarcoma

OBJECTIVES:

Primary

• Determine the median progression-free survival, in terms of stable disease, of patients with newly diagnosed or recurrent/refractory angiosarcoma treated with bevacizumab.

Secondary

• Evaluate the treatment effect of bevacizumab on the objective response rate as assessed by modified RECIST criteria in patients with angiosarcoma.
• Evaluate the duration of response.
• Assess the treatment effect of bevacizumab on duration of overall survival.
• Explore the objective response by target tumor density changes on CT scan.
• Evaluate the safety and tolerability of bevacizumab in patients with angiosarcoma.

OUTLINE: This is an open-label, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 to 4 months for 2 years.

PROJECTED ACCRUAL: A total of 31 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed angiosarcoma

• Any stage disease
• Must be deemed not surgically resectable (complete resection) and/or no other therapeutic modality is known to be curative
• No angiosarcoma of a vessel wall
• Newly diagnosed or recurrent/refractory disease
• No prior tumor-related hemorrhage (any grade)
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
• No CNS disease, brain metastases, or primary brain tumors

PATIENT CHARACTERISTICS:

• ECOG performance status of 0 or 1
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 gm/dL (transfusion and epoetin alfa allowed)
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Urine protein:creatinine ratio ≤ 1.0
• Total bilirubin ≤ 1.5 mg/dL
• Aspartate aminotransferase < 5 times ULN
• Alkaline phosphatase < 5 times ULN
• PT/INR ≤ 1.5 times ULN
• PTT ≤ 1.5 times ULN
• Fertile patients must use effective contraception
• Ejection fraction > 49% for patients with prior anthracycline therapy, ischemic cardiac disease, or history of heart failure
• No uncontrolled active infection
• No uncontrolled high blood pressure (defined as > 150/100 mm Hg)
• No symptomatic congestive heart failure (New York Heart Association class II-IV), unstable angina, cardiac arrhythmia, or myocardial infarction within the past 6 months
• No psychiatric illness or social situation that would limit study compliance
• No serious, nonhealing wound, ulcer, or bone fracture
• No evidence of bleeding diathesis or coagulopathy
• No clinically significant peripheral vascular disease
• Not pregnant or nursing
• No seizures not controlled with standard medical therapy
• No embolic or hemorrhagic stroke or prior transient ischemic attack
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No significant traumatic injury within the past 6 weeks

PRIOR CONCURRENT THERAPY:

• No prior therapy with bevacizumab or other antiangiogenesis treatment
• No major surgical procedure or open biopsy within the past 6 weeks
• No more than 2 prior chemotherapy regimens
• No fine-needle aspiration or core-needle biopsy or other minor surgical procedure within the past 7 days
• No radiotherapy within the past 28 days
• No concurrent chronic daily treatment with aspirin > 325 mg/day or nonsteroidal anti-inflammatory medications
• No concurrent warfarin or any other anticoagulant (any dose)
• No concurrent radiotherapy
• No concurrent major surgery