Paclitaxel + Bevacizumab (Avastin®) for the Treatment of Metastatic or Unresectable Angiosarcoma

Inclusion Criteria:

• Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study. Abnormal PET scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging.
• Patient must have at least one objective measurable disease parameter by RECIST criteria.
• Patients must have unresectable locally advanced or metastatic angiosarcoma.
• Patients must have had <= 2 prior chemotherapeutic regimens for angiosarcoma.
• No prior paclitaxel, docetaxel, or bevacizumab for angiosarcoma. (Previous paclitaxel or docetaxel allowed if not given for angiosarcoma and more than 12 months has elapsed since last dose)
• Patients must not have had evidence of other active malignancies other than carcinomas in-situ of the cervix or basal cell carcinoma of the skin within 6 months prior to registration.
• Patients with a history of deep venous thrombosis or pulmonary embolism must be receiving a stable dose of anticoagulation therapy for at least 2 weeks prior to registration.
• Patients must not have been using any anti-platelet drugs, such as ticlopidine, clopidogrel, and cilostazol, during study or within 7 days prior to registration. The use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) is allowed.
• Patients must have an ECOG performance status 0-2.

• Patients must have adequate organ function as evidenced by the following laboratory studies (within 2 weeks prior to registration):

  • Serum creatinine (<= 2.0 mg/dl)
  • Total bilirubin <= 2.0 x ULN and SGOT (AST) < 2 x ULN. If documented hepatic involvement, total bilirubin can be <= 3 x ULN, and AST <= 5 x ULN.
  • Absolute neutrophil count >= 1500/mm3 and platelet count > 100,000/mm3.
  • PT, INR, and PTT <= 1.5 x normal.
• Patients must not have an active infection requiring parental antibiotics.
• Patients must not have known HIV infection due to increase risk of infection.
• Patients must have a left ventricular ejection fraction >= 50% to be eligible.
• Patients must be age >= 13 years.
• Women must not be pregnant or breast feeding due to potential harmful effects to the fetus/baby. Women of childbearing potential must have an HCG within 2 weeks prior to registration.
• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception.

Exclusion Criteria:

• Inability to comply with study and/or follow-up procedures
• Life expectancy of less than 12 weeks
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an another experimental drug study
• Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix D)
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1

• Known CNS disease, except for treated brain metastasis

  o Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded

• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria as demonstrated by a UPC ratio >= 1.0 at screening
• Known hypersensitivity to any component of bevacizumab