Preoperative Dose-dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab in Operable Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Doxorubicin; Cyclophosphamide; Paclitaxel; Bevacizumab
Intervention description: Standard chemotherapy regimen; Standard chemotherapy regimen; Standard chemotherapy regimen; One intravenous dose given followed 2 weeks later with standard chemotherapy drugs and bevacizumab given intravenously in 8 two-week cycles.
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Bevacizumab; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ER positive; PR positive

Summary:

      Dose dense chemotherapy, which is the term for Adriamycin and Cyclophosphamide (AC) followed
      by Taxol chemotherapy given every two weeks, is the standard chemotherapy for the treatment
      of ER+ or PR+ breast cancer. In this trial, the standard chemotherapy is being combined with
      bevacizumab. Bevacizumab is an antibody which works differently from the way other
      chemotherapy drugs work. Bevacizumab slows or stops cell growth in cancerous tumors by
      decreasing the blood supply to the tumors by binding to a substance found on cancer cells
      called VEGF (vascular endothelial growth factor). Bevacizumab is approved by the FDA for the
      treatment of colorectal cancer and lung cancer. However, it is not approved for the treatment
      of breast cancer. Another goal of this research is to determine whether we can develop a way
      to identify tumors that will respond well to this study treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented primary invasive breast cancer by histologic assessment

          -  Tumors must express estrogen (ER) and/or progesterone receptors (PR) by standard
             immunohistochemical methods. Tumors must be negative for HER2. There must be
             sufficient sample for further protocol-specified immunohistochemical analysis

          -  Patients must have high risk ER+ or PR+ breast cancer as defined by criteria listed in
             protocol

          -  18 year of age or older

          -  Performance status of 0 or 1 by ECOG criteria

          -  Use of an effective means of contraception in subjects of childbearing potential

          -  Women of childbearing potential must have a negative serum pregnancy test within 14
             days prior to starting therapy.

          -  Patients taking exogenous sex-steroid hormone treatments for any reason at the time of
             diagnosis must discontinue all hormonal treatments at least 2 weeks prior to
             enrollment

          -  Patients must have preoperative treatment within 60 days of initial diagnosis of
             breast cancer

          -  No other malignancy that requires on-going treatment

          -  Normal organ function as outlined in the protocol

        Exclusion Criteria:

          -  Prior cytotoxic chemotherapy or radiation for the current breast cancer

          -  Patients with inflammatory breast cancer

          -  HER2 positive disease defined as HER2-amplified by FISH or IHC 3+. HER2 2+ must be
             negative by FISH

          -  Known metastatic (Stage IV) disease

          -  Other investigational agents within 4 weeks prior to the start of study treatment

          -  Life expectancy of less than 6 months

          -  Peripheral neuropathy greater than or equal to grade 2

          -  Inadequately controlled hypertension

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  NYHA grade II or greater congestive heart failure

          -  History of prior myocardial infarction

          -  History of unstable angina within 12 months prior to study enrollment

          -  Any history of stroke or transient ischemic attack at any time

          -  Known CNS disease

          -  Significant vascular disease

          -  Symptomatic peripheral vascular disease

          -  Evidence of significant bleeding within 6 months of study; any serious non-healing
             wound, skin ulcers, or bone fracture; any abdominal fistula, gastrointestinal
             perforation or intra-abdominal abscess within the past 6 months; any major surgical
             procedure within 28 days prior to randomization or anticipation of need for major
             surgery during course of study.

          -  Known HIV positive

          -  Unwilling to undergo pretreatment biopsy and consent to acquisition of archival tissue

          -  Pregnant of lactating

          -  Known hypersensitivity to any component of bevacizumab