Preoperative Cisplatin and Bevacizumab in ER-, PR-, HER2 Negative Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: cisplatin; bevacizumab; doxorubicin; cyclophosphamide; paclitaxel
Intervention description: Preoperatively: Given intravenously on day one of the treatment cycle (once every 3 weeks) for four cycles; Preoperatively: Given intravenously on day 1 of the treatment cycle (once every three weeks) for three cycles Postoperatively: Intravenously for four 2-week cycles (once every two weeks) and after the 8 weeks (study doctor will determine course of treatment) for an additional four 2-week cycles with or with out paclitaxel; Postoperative: Given intravenously for four 2-week cycles; Postoperative: Given intravenously for four two-week cycles; Postoperative: 8 weeks after postoperative chemotherapy regimen (study doctor will determine course of treatment) paclitaxel for four 2-week cycles (once every two weeks)
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Bevacizumab; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ER negative; PR negative; HER2 negative

Summary:

      The purpose of this study is to find out what effect taking cisplatin in combination with
      bevacizumab before surgery and then standard chemotherapy plus bevacizumab after surgery will
      have on participants with Estrogen Receptor (ER) negative, Progesterone Receptor (PR)
      negative and Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer.
      Cisplatin is used to destroy cancer cells in many types of cancers, and has shown to be
      effective and have manageable side effects. Bevacizumab is an antibody, which is a protein
      that attacks a foreign substance in the body. Bevacizumab slows or stops cell growth in
      cancerous tumors by decreasing the blood supply to the tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All tumors must be ER-, PR- and HER2-negative

          -  Clinical stage T2 or T3, N0-3, M0. Subjects with inflammatory breast cancer are not
             eligible

          -  For subjects with clinically negative axilla, a sentinel lymph node biopsy will be
             performed either up front or after preoperative therapy at the discretion of the
             subject's physicians; for subjects with a clinically positive axilla, a needle
             aspiration or core biopsy will be performed to confirm the presence of metastatic
             disease in the lymph nodes.

          -  18 years of age or older

          -  Performance status (PS) of 0 or 1

          -  Use of an effective means of contraception in subjects of child-bearing potential

          -  Normal organ function as described in the protocol

        Exclusion Criteria:

          -  Any prior cytotoxic chemotherapy or radiation for the current breast cancer

          -  HER2-negative ipsilateral breast recurrence, unless prior treatment consisted of
             excision alone for ductal carcinoma in situ (DCIS)or breast-conserving treatment and
             hormonal therapy for DCIS or invasive cancer

          -  Life expectancy of less than 12 weeks

          -  Current, recent, or planned participation in an experimental durg study other than a
             Genentech-sponsored bevacizumab cancer study

          -  Renal dysfunction for which exposure to cisplatin would require dose modifications

          -  Steroid dependent asthma

          -  Peripheral neuropathy of any etiology that exceeds grade 1

          -  Uncontrolled diabetes

          -  History of malignancy treated without curative intent

          -  Any other pre-existing medical condition that would represent toxicity in excess of
             grade 1

          -  Inadequately controlled hypertension

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive hear failure

          -  History of myocardial infarction or unstable angina within 12 months prior to study
             enrollment

          -  Any history of stroke or transient ischemic attack at any time

          -  Known central nervous system (CNS) disease

          -  Significant vascular disease

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 21 days
             prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious, non-healing wound, ulcer or bone fracture

          -  Proteinuria at screening

          -  Known hypersensitivity to any component of bevacizumab

          -  Pregnant or lactating