Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU
Condition: Breast Carcinoma; Recurrent Breast Carcinoma; Stage IV Breast Cancer
MeSH terms: Carcinoma; Breast Neoplasms
Intervention: Bevacizumab; Carboplatin; Paclitaxel; Placebo; Trastuzumab
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Trastuzumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Trastuzumab; Bevacizumab; Metastatic Breast Cancer; HER2/NEU

Summary:

      This randomized phase III trial studies first-line chemotherapy and trastuzumab to compare
      how well they work when given with or without bevacizumab in treating patients with breast
      cancer that overexpresses human epidermal growth factor receptor 2 (HER-2/NEU) and has spread
      to other areas of the body. Drugs used in chemotherapy, such as paclitaxel and carboplatin,
      work in different ways to stop the growth of tumor cells, either by killing the cells, by
      stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such
      as trastuzumab and bevacizumab, may interfere with the ability of tumor cells to grow and
      spread. Bevacizumab may also stop the growth of breast cancer by blocking the growth of new
      blood vessels necessary for tumor growth. It is not yet known whether giving first-line
      chemotherapy together with trastuzumab is more effective with or without bevacizumab in
      treating patients with metastatic breast cancer that overexpresses HER-2/NEU.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed breast cancer that overexpresses HER-2/NEU with evidence of
             metastatic disease and/or chest wall recurrence prior to randomization

          -  HER-2/NEU overexpression is defined as 3+ HER-2 positivity as measured by
             immunohistochemistry OR HER-2 gene amplification as measured by fluorescent in situ
             hybridization (FISH, e.g. Vysis), per American Society of Clinical Oncology guidelines

               -  NOTE: representative diagnostic tissue must be submitted for central diagnostic
                  review for confirmation of HER-2/NEU overexpression within two weeks following
                  patient randomization

          -  Evaluable (measurable or non-measurable) disease is allowed if confirmed within 4
             weeks prior to randomization

          -  Prior endocrine treatment in the adjuvant or metastatic setting is allowed, provided
             last dose given >= 2 weeks prior to randomization

          -  Radiation therapy is allowed provided last dose is given >= 3 weeks prior to
             randomization

          -  Adjuvant trastuzumab therapy for breast cancer is allowed provided last dose was given
             >= 12 months prior to diagnosis of recurrence

          -  Adjuvant or neoadjuvant taxane therapy for breast cancer is allowed provided last dose
             was given >= 12 months prior to diagnosis of recurrence

          -  Adjuvant or neoadjuvant therapy with lapatinib is allowed provided last dose is given
             >= 4 weeks prior to diagnosis of recurrence

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Absolute neutrophil count >= 1,000/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Total bilirubin =< 1.5 mg/dL

          -  Aspartate aminotransferase (AST) =< 2 times upper limit of normal (ULN) (=< 5 times
             normal in patients with known liver involvement)

          -  Serum creatinine =< 1.5 mg/dL

          -  Urine protein: creatinine ratio =< 0.5 OR 24-hour urine protein < 1000 mg

          -  International normalized ratio (INR) =< 1.5 X ULN

          -  Partial thromboplastin time (PTT) =< 1.5 X ULN

          -  Multi gated acquisition scan (MUGA) scan or echocardiogram (ECHO) within 6 weeks prior
             to randomization with an left ventricular ejection fraction (LVEF) above the
             institutional lower limit of normal

          -  Patients must be able to understand and provide signed and dated written informed
             consent

          -  Major surgical procedure within 4 weeks prior to randomization is not allowed (except
             for non-operative biopsy, which would not be considered major surgery); treatment can
             not begin until seven (7) days after placement of a vascular access device

          -  Women must not be pregnant or breastfeeding; all females of childbearing potential
             must have a blood or urine test within 2 weeks prior to randomization to rule out
             pregnancy; women of childbearing potential and sexually active males must use an
             accepted and effective method of contraception

          -  Patients on full-dose anticoagulants (e.g., warfarin) with PT/INR > 1.5 may be
             eligible provided that both of the following criteria are met:

               -  The patient has an in-range INR (usually between 2 and 3) on a stable dose of
                  oral anticoagulant or on a stable dose of low molecular weight heparin

               -  The patient has not active bleeding or pathological condition that carries a high
                  risk of bleeding (e.g., tumor involving major vessels or known varices)

          -  Patients with a concurrent active malignancy except carcinoma in situ of the cervix or
             non-melanoma skin cancers (unless disease-free for at least 5 years at study entry)
             are not allowed

        Exclusion Criteria:

          -  Prior chemotherapy, trastuzumab, or bevacizumab for metastatic breast cancer

          -  Patients who have had a cumulative dose of doxorubicin of greater than 360 mg/m^2 or
             epirubicin of greater than 640 mg/m^2 in the adjuvant or neo-adjuvant setting at any
             time

          -  Patients with grade 2-4 neuropathy

          -  Patients with a history or radiologic evidence of central nervous system (CNS) disease

          -  Patients have a current non-healing wound or fracture

          -  Patients have a hypersensitivity to paclitaxel or drugs using the vehicle Cremophor,
             Chinese hamster ovary cell products or other recombinant human antibodies

          -  Patients have a serious medical or psychiatric illness that would prevent ability to
             safely participate or provide informed consent

          -  Patients using any of the following drugs known to inhibit platelet function are not
             eligible: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and
             cilostazol (Pletal)

          -  Clinically significant cardiovascular disease, including:

               -  History of cerebrovascular (CVA) within 6 months

               -  Uncontrolled hypertension

               -  Myocardial infarction or unstable angina within 6 months

               -  New York Heart Association class II or greater congestive heart failure, serious
                  cardiac arrhythmia requiring medication, unstable angina pectoris

               -  Clinically significant peripheral vascular disease