Carboplatin, Paclitaxel, and Bevacizumab in Treating Patients With Locally Recurrent or Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: bevacizumab; Carboplatin; ABI-007
Intervention description: Participants will receive bevacizumab 15 mg/kg on days 1,22, and 43.; Participants will receive a standard carboplatin dose according to their area under the plasma drug concentration-time curve (AUC-6) on days 1, 22, and 43.; Participants will receive ABI-007 (Abraxane) 100mg/m2 on days 1,8, 15, 22, 29, 36,43,and 50.
Intervention MeSH terms: Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent breast cancer; stage III breast cancer; stage IV breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized
      nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Monoclonal antibodies, such as
      bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells
      to grow and spread. Others find tumor cells and help kill them or carry cancer-killing
      substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood
      flow to the tumor. Giving carboplatin and paclitaxel together with bevacizumab may kill more
      tumor cells.

      PURPOSE: This phase II trial is studying how well giving carboplatin and paclitaxel together
      with bevacizumab works in treating patients with locally recurrent or metastatic breast
      cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed primary adenocarcinoma of the breast

               -  Locally recurrent or metastatic disease

          -  Must have HER-2-negative breast cancer or, if HER-2-positive, must be unable to
             receive trastuzumab (Herceptin®) or have previously received trastuzumab in the past

          -  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 by conventional
             techniques or as > 10 mm by spiral CT scan.

          -  No known CNS disease

          -  Hormone receptor status not specified

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  Postmenopausal status not specified

          -  ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%

          -  Life expectancy > 12 weeks

          -  WBC ≥ 3,000/mcL

          -  Absolute neutrophil count ≥ 1,500/mcL

          -  Platelet count ≥ 100,000/mcL

          -  Total bilirubin normal

          -  AST and ALT ≤ 2.5 times upper limit of normal (ULN)

          -  Alkaline phosphatase ≤ 2.5 times ULN (unless bone metastasis is present in the absence
             of liver metastasis)

          -  Creatinine ≤ 1.5 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No other concurrent malignancies within the past 5 years except basal cell or squamous
             cell skin cancer or carcinoma in situ of the cervix

        Exclusion criteria:

          -  Pre-existing neuropathy ≥ grade 1

          -  Uncontrolled intercurrent illness including, but not limited to, any of the following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Serious, non-healing wound, ulcer, or bone fracture

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 mm Hg
             and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications)

          -  History of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association class II-IV congestive heart failure

          -  History of myocardial infarction or unstable angina within the past 6 months

          -  History of stroke or transient ischemic attack within the past 6 months

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Significant traumatic injury within the past 28 days

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within the past 6 months

          -  Proteinuria, as demonstrated by either urine protein:creatinine ratio ≥ 1.0 OR urine
             dipstick for proteinuria ≥ 2+

               -  Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline
                  must demonstrate 24-hour urine protein ≤ 1g

          -  History of allergy or hypersensitivity to paclitaxel albumin-stabilized nanoparticle
             formulation, paclitaxel, bevacizumab, carboplatin, albumin, drug product excipients,
             or chemically similar agents

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Recovered from all prior therapy

          -  No prior chemotherapy for locally recurrent or metastatic disease

          -  Prior neoadjuvant or adjuvant chemotherapy allowed

          -  More than 1 week since prior core biopsy or other minor surgical procedure, excluding
             placement of a vascular access device

          -  More than 4 weeks since prior and no concurrent major surgical procedure or open
             biopsy

          -  More than 4 weeks since prior radiotherapy

          -  More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

          -  At least 1 year since prior taxane regimen

          -  No other concurrent investigational agents

          -  Concurrent anticoagulation allowed, provided the following criteria are met:

               -  Stable dose of warfarin or low molecular weight heparin

               -  INR within desired range (2-3)

               -  No evidence of active bleeding or coagulopathy

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No other concurrent radiotherapy, chemotherapy, immunotherapy, or antitumor hormonal
             therapy