Bevacizumab and Combination Chemotherapy in Patients With Lymph Node Positive Breast Cancer
Condition: Male Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer
MeSH terms: Breast Neoplasms; Breast Neoplasms, Male
Intervention: doxorubicin hydrochloride; cyclophosphamide; bevacizumab; paclitaxel; filgrastim; pegfilgrastim; radiation therapy; tamoxifen citrate; aromatase inhibition therapy
Intervention description: Given IV; Given IV; Given IV; Given IV; Given SC; Given SC; Undergo radiation therapy; Given orally; Receive aromatase inhibition therapy
Intervention MeSH terms: Tamoxifen; Cyclophosphamide; Bevacizumab; Doxorubicin; Liposomal doxorubicin; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim; Aromatase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 226.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bevacizumab together with combination
      chemotherapy works in treating patients who have undergone surgery for breast cancer that has
      spread to the lymph nodes. 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 tumor-killing substances to them. Bevacizumab may
      also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in
      chemotherapy work in different ways to stop the growth of tumor cells, either by killing the
      cells or by stopping them from dividing. Giving bevacizumab together with more than one
      chemotherapy drug (combination chemotherapy), may be a better way to block tumor growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the breast with involvement of at least one
             axillary or internal mammary lymph node on routine histologic examination with
             hematoxylin and eosin staining; NOTE: patients with axillary or internal mammary node
             involvement only demonstrated by immunohistochemistry are not eligible

          -  Patients must have completed definitive breast surgery including total mastectomy and
             axillary dissection (modified radical mastectomy), total mastectomy and sentinel node
             biopsy, lumpectomy and axillary dissection, or lumpectomy and sentinel node biopsy;
             NOTE: axillary dissection is strongly encouraged in patients with lymph node
             involvement identified on sentinel node biopsy

          -  Margins of lumpectomy or mastectomy must be histologically free of invasive breast
             cancer and ductal carcinoma in situ (DCIS); patients with resection margins positive
             for lobular carcinoma in situ (LCIS) are eligible

          -  (ARM A ONLY) Interval between last surgery for breast cancer (lumpectomy, mastectomy,
             sentinel node biopsy, axillary dissection or re-excision of lumpectomy margins) and D1
             must be > 28 days and =< 84 days

          -  ECOG performance status of 0-2

          -  Absolute neutrophil count >= 1000/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Total bilirubin =< 1.5 mg/dL

          -  AST =< 2 upper limit of normal

          -  Serum creatinine =< 1.5 mg/dL

          -  Urine protein: creatinine ratio < 1.0

          -  PT INR =< 1.5

          -  PTT =< 1.5 x normal

          -  LVEF >= institutional limits of normal by MUGA or ECHO

          -  Prior to registration the investigator must specify if radiation is planned; patients
             who have undergone a lumpectomy must receive radiation; post-mastectomy radiation is
             at the investigator's discretion

          -  Patients with HER2+ (3+ by IHC or FISH+) breast cancer are not eligible and should be
             treated with a trastuzumab-based adjuvant therapy

          -  Patients with synchronous bilateral breast cancer (diagnosed within one month) are
             eligible if the higher TMN stage tumor meets the eligibility criteria for this trial

          -  Patients must not have clinical evidence of inflammatory disease or fixed axillary
             nodes (N2) at diagnosis

          -  Patients must not have received prior cytotoxic chemotherapy, hormonal therapy or
             radiation for this breast cancer; prior treatment with an anthracycline,
             anthracenedione or taxane for any condition is not allowed; NOTE: prior use of
             tamoxifen for chemoprevention is allowed but must be discontinued at study entry;
             similarly prior raloxifene use is allowed but must be discontinued at study entry

          -  Patients must not have had a major surgical procedure within 4 weeks of entry; NOTE:
             non-operative biopsy or placement of a vascular access device is not considered a
             major surgery

          -  Patients must not have clinically significant cardiovascular disease including:

               -  New York Heart Association (NYHA) grade II or greater congestive heart failure

               -  Grade II or greater peripheral vascular disease

               -  Uncontrolled hypertension defined as SBP > 160 or DBP > 90

               -  Any prior history of cerebrovascular disease including TIA or stroke

          -  Patients must not require therapeutic anticoagulation; patients with a history of deep
             venous thrombosis or pulmonary embolism are not eligible; NOTE: prophylactic use of
             anticoagulants to maintain patency of a vascular assess device is permitted

          -  Patients may not require regular use of aspirin (daily for >= 10 days at doses of >
             325 mg/day) or regular therapeutic doses of other nonsteroidal anti-inflammatory
             agents known to inhibit platelet function; additionally, patients using any of the
             following drugs known to inhibit platelet function are not eligible: dipyridamole
             (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal);
             NOTE: regular use of Cox-2 inhibitors is permitted; NOTE: low-dose aspirin is
             permitted

          -  Patients must not have a non-healing wound or fracture; patients with an abdominal
             fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months are
             excluded

          -  Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle
             Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies

          -  Patients who have experienced myocardial infarction or unstable angina within 12
             months are excluded

          -  Patients who have had experienced an arterial thrombotic event within 12 months are
             excluded

          -  Patients must not have uncontrolled or clinical significant arrhythmia

          -  Women must not be pregnant or breast-feeding due to the potential harmful effects of
             bevacizumab on the developing fetus; all females of childbearing potential must have a
             blood test or urine study within 2 weeks prior to registration to rule out pregnancy

          -  Women of childbearing potential and sexually active males are required to use an
             accepted and effective method of contraception while on study and for at least 3-4
             months after the last dose of bevacizumab