Paclitaxel in Combination With Bevacizumab (Avastin®) for the Treatment of Metastatic or Unresectable Angiosarcoma
- 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
- 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
- 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
- Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception.
- 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
- 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
- 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
- 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