Paclitaxel + Bevacizumab (Avastin) for the Treatment of Metastatic or Unresectable Angiosarcoma
Condition: Angiosarcomas; Soft Tissue Sarcoma
MeSH terms: Sarcoma; Hemangiosarcoma
Intervention: Bevacizumab; Paclitaxel
Intervention description: 15 mg/kg, IV every 21 days x 6 cycles.; Regimen A / Treatment 1: 200 mg/m² IV over 3 hours every 21 days.
Regimen B / Treatment 2: 90 mg/m² weekly x 3 of a 28-day cycle
Intervention MeSH terms: Paclitaxel; Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is an open-label, single-arm, multi-center, Phase 2 study with Paclitaxel in combination
      with Bevacizumab in patients with Unresectable or Metastatic Angiosarcoma. The study aims to
      determine the safety and effectiveness of combining two drugs Paclitaxel and Bevacizumab in
      the treatment of Angiosarcoma that cannot be removed by surgery, or has spread to other parts
      of your body. The primary objective is to evaluate 4month non progression rate. The secondary
      objective is to evaluate overall response rate after 3rd and 6th cycle, median duration of
      response, 6th and 12th month survival, toxicity of Paclitaxel and Bevacizumab combination,
      toxicity of maintenance Bevacizumab and to collect paraffin-embedded tumor blocks for
      angiogenesis markers and tissue microarray.
    

Eligibility criteria:

        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 computed tomography (CT) scan or other appropriate imaging

          -  At least 1 objective measurable disease parameter by Response Evaluation Criteria In
             Solid Tumors (RECIST) criteria

          -  Unresectable locally advanced or metastatic angiosarcoma

          -  ≤ 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)

          -  No 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

          -  If history of deep venous thrombosis or pulmonary embolism, receiving a stable dose of
             anticoagulation therapy for at least 2 weeks prior to registration

          -  Within 7 days prior to registration, use of any anti-platelet drugs, such as
             ticlopidine, clopidogrel, and cilostazol. The use of aspirin or other nonsteroidal
             anti-inflammatory drugs (NSAID) is allowed

          -  ECOG performance status 0 to 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 upper limit of normal (ULN). If documented hepatic
             involvement, can be ≤ 3 x ULN

          -  Serum glutamic oxaloacetic transaminase (SGOT) or Aspartate aminotransferase (AST) < 2
             x ULN. If documented hepatic involvement, can be ≤ 5 x ULN

          -  Absolute neutrophil count ≥ 1500/mm3 and platelet count > 100,000/mm3

          -  Platelets ≤ 1.5 x ULN

          -  International normalized ratio (INR) ≤ 1.5 x ULN

          -  Partial thromboplastin time (PTT) ≤ 1.5 x ULN

          -  Left ventricular ejection fraction ≥ 50%

          -  ≥ 18 years

          -  Women of childbearing potential must have a negative human chorionic gonadotropin
             (hCG) pregnancy test within 2 weeks prior to registration

        EXCLUSION CRITERIA

          -  Life expectancy < 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)

          -  History of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  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 central nervous system (CNS) disease, except for treated brain metastasis.
             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 (eg, 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 urine protein: creatinine ratio (UPC) ratio ≥ 1.0 at
             screening

          -  Known hypersensitivity to any component of bevacizumab

          -  Active infection requiring parental antibiotics

          -  Known human immunodeficiency virus (HIV) infection

          -  Pregnant or breast feeding

          -  Inability to comply with study and/or follow-up procedures