ABI-007 In Combination With Bevacizumab in Women With Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: ABI-007; Bevacizumab
Intervention description: 125 mg/m^2 of ABI-007 administered by intravenously (IV) over 30 minutes on days 1, 8 and 15 of each 28 day cycle.; Bevacizumab administered once every 2 weeks (10 mg/kg) by IV infusion after ABI-007 has been given. The first dose is one Day 1, cycle 1.
Intervention MeSH terms: Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic breast cancer, Abraxane, Bevacizumab

Summary:

      The purpose of this study is to evaluate the safety and tolerability of weekly ABI-007 in
      combination with bevacizumab.

      The evaluation of progression-free survival of weekly ABI-007 in combination with bevacizumab
      for patients with previously untreated advanced/metastatic breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed adenocarcinoma of the breast.

          -  Stage IV disease.

          -  Measurable disease (defined as the presence of at least one lesion that can be
             accurately measured in at least one dimension with longest diameter greater or = 1.0
             cm with spiral computed tomography (CT) scan).

          -  Patients must not be a candidate for Herceptin therapy (i.e., patients with HER-2
             positive disease (gene amplification by fluorescence in situ hybridization (FISH) or 3
             + overexpression by ICH) and patients with unknown HER-2 status are ineligible unless
             the treating physicians has determined that Herceptin-based therapy would be
             inappropriate or not indicated).

          -  For subjects with prior anthracycline exposure, normal cardiac function including a
             baseline left ventricle ejection fraction >50% or above institution's lower limit of
             normal and a normal electrocardiogram (ECG) (as assessed by the investigator).

          -  At least 2 weeks since radiotherapy, with full recovery. The measurable disease must
             be completely outside the radiation portal or there must be pathologic proof of
             progressive disease within the radiation portal.

          -  International Normalized Ratio (INR) < 1.5 and activated partial thromboplastin time
             within normal limits (APTT WNL).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          -  Female > 18 years of age.

          -  Patients have the following blood counts at Baseline: absolute neutrophil count (ANC)
             greater or equal to 1.5 x 10^9 cells/L; platelets greater or equal 100 x 10^9 cells/L;
             hemoglobin (Hgb) greater or equal to 9g/dL.

          -  Patients have the following blood chemistry levels at Baseline: aspartate
             aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT) less than or
             equal 2.5x upper limit of normal (ULN) range (less than or equal 5x ULN if patient has
             known liver metastases); total bilirubin greater than or equal to ULN; creatinine
             greater or equal to 1.5mg/dL.

          -  if female of childbearing potential, pregnancy test is negative within 72 hours of
             first dose of study drug.

          -  if fertile, the patient agrees to use an effective method to avoid pregnancy for the
             duration of the study.

          -  Informed consent has been obtained.

        Exclusion Criteria:

          -  No prior chemotherapy for metastatic or locally recurrent disease is allowed.

          -  Prio neo-adjuvant chemotherapy is allowed, and patients must have recovered from the
             acute toxicity of such therapies.

               -  if a taxane was part of the adjuvant regimen, at least 12 months must have
                  elapsed between the last dose of the taxane and the date of diagnosis of
                  metastatic disease.

               -  if a non-taxane-based adjuvant therapy was administered, at least six months must
                  have elapsed between the last dose of the non- taxane-containing chemotherapy and
                  the date of diagnosis of metastatic disease.

          -  Concurrent immunotherapy or hormonal therapy.

          -  Parenchymal brain metastases, including leptomeningeal involvement.

          -  Uncontrolled hypertension (defined as blood pressure of > 150/100 mmHg)

          -  NYHA Grade 2 or greater congestive heart failure

          -  History of coagulopathy, bleeding diathesis, therapeutic anticoagulation other than
             low dose or chronic ASA greater than or equal to 325 mg per day. Low dose coumadin for
             anticoagulation of venous access device or low dose molecular weight heparin (LMWH)for
             deep vein thrombosis prophylaxis or low dose (325 mg or less) ASA prophylaxis are
             allowed, but are best avoided if the treating physician feels it is safe to do so.

          -  Urine protein:creatinine ratio less than or equal to 1.0 at screening.

          -  No history of cerebrovascular accident within six months of study entry.

          -  Active symptomatic peripheral vascular disease (e.g. aortic aneurysm, claudication)
             within six months of study entry.

          -  Uncontrolled or severe cardiovascular disease including myocardial infarction or
             unstable angina within six months of study entry.

          -  No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
             process within six months of study entry.

          -  No serious non-healing wound, ulcer, or bone fracture

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to first dose, or anticipation of need for major surgical procedure during the
             course of the study. No minor surgical procedure within seven days of study entry.
             Serious intercurrent medical or psychiatric illness, including serious active
             infection.

          -  History of other malignancy within the last 5 years which could affect the diagnosis
             or assessment of breast cancer.

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study.

          -  Pregnant or nursing women.

          -  Patients with current sensory neuropathy of > Grade 1 will be excluded.