Preoperative Cisplatin and Bevacizumab in ER-, PR-, HER2 Negative Breast Cancer
Preoperative Cisplatin and Bevacizumab in ER-, PR-, HER2 Negative Breast Cancer
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.
-  To prepare for surgery, a small "clip" will be placed into the tumor area so that the
 surgeon can locate the site of the tumor at the time of surgery. This is a standard
 procedure for breast cancer.

 -  The study drugs will be given in four 3-week cycles (about 3 months). Participants will
 come into the clinic each day they receive study treatment intravenously. Cisplatin will
 be given on day one of the treatment cycle (once every 3 weeks) for four cycles.
 Bevacizumab will be given on day one of the treatment cycle for three cycles.

 -  On day one of each 3-week cycle a physical exam, routine blood tests and urine test will
 be performed. 7-8 days after chemotherapy, blood tests and a hearing test will be
 performed. A preoperative study visit will take place 7-10 days before surgery and a
 physical exam, routine blood tests, Electrocardiogram (EKG) and an Magnetic Resonance
 Imaging (MRI) of the breast will be performed.

 -  Surgery to remove the tumor will occur at least three weeks after the last dose of
 cisplatin and is considered standard of care.

 -  Postoperative chemotherapy will begin at least three weeks after surgery. Everyone on
 the research study will receive four 2-week cycles of doxorubicin and cyclophosphamide
 plus bevacizumab. After the 8 weeks, the doctor will decide which of the following two
 treatment regimens the participant will receive: Bevacizumab for four 2-week cycles
 (once every two weeks) or; Paclitaxel plus bevacizumab for four 2-week cycles (once
 every two weeks).

 -  At the end of the postoperative chemotherapy, the participant will return to the clinic
 for a medical history, physical exam, vital signs, performance status, routine blood
 tests, multiple gated acquisition scan (MUGA) or Echocardiogram Scans, and a hearing
 test.
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