Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer
Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer
This is a phase IIb, randomized, parallel-group, noncomparative, multicenter, pilot study
 designed to evaluate the safety and efficacy of bevacizumab with or without (+/-) trastuzumab
 administered with three different docetaxel-based combination regimens for the adjuvant
 treatment of participants with node positive or high-risk node negative breast cancer.
In this study, participants were stratified according to HER2 status at the time of
 enrollment. HER2-negative participants were randomized in a 1:1 ratio to either stratum 1
 (AC->T sequential + bevacizumab) or stratum 2 (TAC + bevacizumab). All HER2-positive
 participants were assigned to stratum 3 (TCH + bevacizumab).

 The study included a treatment period of 1 year, followed by a 2 year posttreatment survival
 follow-up period.
The following information on clinical trials is provided for information purposes only to
 allow participants and physicians to have an initial discussion about the trial. This
 information is not intended to be complete information about the trial, to contain all
 considerations that may be relevant to potential participation in the trial, or to replace
 the advice of a personal physician or health professional.

 Inclusion Criteria:

 -  Women >/= 18 years of age.

 -  Histologically proven breast cancer with an interval between definitive breast surgery
 that includes axillary lymph node (LN) dissection or axillary nodal evaluation and
 study registration of < 60 days. (Note: Cycle 1 of chemotherapy treatment may NOT be
 infused until > 28 days after the date of definitive breast surgery and the
 participant must be recovered from any clinically significant toxicity thereof.)

 -  Definitive surgical treatment must be either mastectomy, or breast conserving surgery
 with axillary lymph node dissection (axillary lymph node evaluation can be either full
 axillary node dissection or sentinel LN evaluation followed by dissection if sentinel
 LN is positive) for operable breast cancer (pT1-4 [including inflammatory], pNO-3, and
 MO). Margins of resected specimen from definitive surgery must be histologically free
 of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma
 in-situ does not count as a positive margin.

 -  Subjects must be either lymph node-positive (pN1-3) or lymph node-negative (pN0) with
 high-risk features as determined by Investigator.

 -  High-risk, lymph node-negative participants, (pN0) will be defined as subjects having
 invasive adenocarcinoma with either a negative sentinel node biopsy (pN0[sn]) OR
 negative lymph node dissection (pN0) disease AND tumor size > 2 cm or tumor size >/= 1
 cm with at least one of the following factors:

 -  negative estrogen receptor (ER) and negative progesterone receptor (PR) status

 -  histologic and/or nuclear Grade 2-3; or

 -  age < 35 years

 -  HER2/neu positive or negative tumors are eligible. HER2 positivity must be documented
 by fluorescence in situ hybridization (FISH).

 -  Estrogen and progesterone receptor status must be performed on the primary tumor prior
 to study entry. Results must be pending or known at the time of study entry.

 -  Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF)
 or shortening fraction (multiple-gated acquisition [MUGA] scan or echocardiography
 respectively). The result must be greater than the lower limit of normal (LLN) for the
 institution.

 -  Hematology evaluation within 2 weeks prior to study entry:

 -  Absolute neutrophil count (ANC) >/= 1,500/μL

 -  Platelets >/= 100,000/μL

 -  Hemoglobin >/= 9 g/dL

 -  Hepatic function evaluation within 2 weeks prior to study entry:

 -  Total bilirubin </= ULN for the institution

 -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be in
 the acceptable range.

 -  Complete staging work-up as follows: All subjects must have an appropriate
 radiographic evaluation, e.g., computed tomography (CT), positron emission tomography
 (PET)/CT, and/or (magnetic resonance imaging) MRI of the brain, chest, abdomen and
 pelvis, and imaging of bone by either a bone scan or PET scan. In cases of positive
 bone imaging, a bone X-ray or MRI evaluation is mandatory to rule out the possibility
 of metastatic bone scan disease. Other tests may be performed as clinically indicated.
 It is recommended that all baseline staging should be completed within 35 days prior
 to study entry.

 Exclusion Criteria:

 -  Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy,
 chemotherapy).

 -  Prior anthracycline therapy, taxoids or platinum salts for any malignancy.

 -  Prior radiation therapy for breast cancer or any radiotherapy to the chest wall for
 any other malignancy.

 -  Bilateral invasive breast cancer.

 -  Pregnant or lactating subjects

 -  Cardiac disease or risk for same as judged by Investigator

 -  Other serious illness or medical conditions such as (partial list- review with
 Investigator) history of significant neurologic or psychiatric disorders that would
 prohibit the understanding and giving of informed consent, active uncontrolled
 infection, active peptic ulcer, unstable diabetes mellitus or subjects with
 symptomatic, intrinsic lung disease resulting in dyspnea at rest

 -  Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other
 selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention
 of breast cancer. Subjects must have discontinued these agents prior to study entry.

 -  Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must
 be stopped prior to study entry.

 -  Concurrent treatment with other experimental drugs. Participation in another clinical
 trial with any investigational non-marketed drug within 30 days prior to study entry.

 -  Concurrent treatment with any other anti-cancer therapy.

 -  Male subjects, as no clinical efficacy or safety data are available from phase I-II
 studies.

 -  Chemotherapy and/or bevacizumab may not be given until > 7 days following a minor
 surgical procedure. Chemotherapy may be given without bevacizumab in circumstances in
 which the participant has recovered sufficiently to receive chemotherapy but has not
 yet reached a 28 day time point at which bevacizumab could be administered.