Trastuzumab and Pertuzumab or Bevacizumab With Combination Chemotherapy in Treating Patients With Stage II-III Breast Cancer
Condition: Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: trastuzumab; Pertuzumab; docetaxel; carboplatin; doxorubicin; cyclophosphamide; paclitaxel; Bevacizumab
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Docetaxel; Cyclophosphamide; Bevacizumab; Carboplatin; Doxorubicin; Liposomal doxorubicin; Trastuzumab; Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well trastuzumab and pertuzumab or bevacizumab with
      combination chemotherapy works in treating patients with stage II-III breast cancer.
      Monoclonal antibodies, such as trastuzumab, pertuzumab, and bevacizumab, can block tumor
      growth in different ways. Some block the ability of tumors to grow and spread. Others find
      tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in
      chemotherapy, such as docetaxel, carboplatin, doxorubicin hydrochloride, cyclophosphamide,
      and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing
      the cells or by stopping them from dividing. Giving trastuzumab and pertuzumab or a
      commercially marketed formulation of bevacizumab without modification with combination
      chemotherapy may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the breast, with sufficient tissue
             available for estrogen receptor (ER), progesterone receptor (PR), and HER 2 testing

               -  HER2 must be positive by IHC or ISH testing by laboratory standard.

          -  Needle biopsy or incisional biopsy

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

          -  Resectable disease-clinical stage I (T/0/N0miT1N0-N0mi), IIA-IIIA (T2 N0/T3N0 or T1-3
             N1-N2a) or unresectable disease - clinical stage IIIB/IIIC (T4 or T1-3 N2b-3); no
             evidence of metastatic disease

          -  No prior chemotherapy, hormonal therapy, or radiation therapy for this cancer

          -  Absolute neutrophil count (ANC) ≥1000/ul

          -  Platelet count ≥ 100,000/ul

          -  Hemoglobin ≥ 9 g/dl

          -  Serum creatinine ≤ 1.5 mg/dl or measured creatinine clearance of > 30 ml/min

          -  Total bilirubin ≤ upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) ≤ 2.5 x ULN

          -  Patients with multiple foci of invasive cancer in the same breast are eligible if any
             single lesion meets the above size criteria and all sampled lesions are histologically
             similar (whether radiographically detected lesions separate from the target lesion are
             sampled for histologic evaluation is left to the discretion of the treating
             physicians); the presence of ductal carcinoma in situ (DCIS) or lobular carcinoma in
             situ (LCIS) in either breast will not render a patient ineligible; patients with a
             small focus of invasive cancer detected the contralateral breast (clinical T1N0) are
             eligible, however only the histologic response in the breast containing the target
             lesions will be considered in determining the patient's pathologic response

          -  Measurable disease in the breast or axilla that measures at least 1 cm by either
             clinical or radiographic measurement

        Exclusion Criteria:

          -  Excisional biopsy

          -  Pregnant and lactating women are not eligible; all participants of reproductive age
             must have a negative serum pregnancy test at baseline and agree to use an effective
             barrier method of contraception during the entire period of treatment on the study

          -  Patients with New York Heart Association (NYHA) grade 2 or higher congestive heart
             failure, myocardial infarction within the last 6 months, unstable angina pectoris, or
             arterial thrombotic event with the past 12 months, uncontrolled hypertension (systolic
             blood pressure > 150 and/or diastolic blood pressure > 100 on antihypertensive
             medications; patients not on medication for high blood pressure who are found to have
             systolic blood pressure [SBP] > 150 and/or diastolic blood pressure [DBP] > 100 should
             have 3 documented episodes of elevated blood pressure before being considered
             'uncontrolled', if they have 3 documented episodes of elevated blood pressure, then
             can be started on antihypertensive medications; patients currently on antihypertensive
             medications with elevated blood pressures as defined above may have their medications
             adjusted; if patients have persistent [3 episodes] of high blood pressure despite
             medication adjustment they will be considered ineligible for study participation; each
             measured episode should be 24 hours apart), prior history of hypertensive crisis or
             hypertensive encephalopathy, uncontrolled or clinically significant arrhythmia, grade
             II or greater peripheral vascular disease or prior history of stroke or transient
             ischemic attack (TIA); patient must have a pretreatment multi gated acquisition scan
             (MUGA) scan or echocardiogram with left ventricular ejection fraction (LVEF) above
             lower limit of normal

          -  No non-breast malignancy within the past 5 years other than treated squamous or basal
             cell carcinoma of the skin or CIS of the cervix

          -  Patients known to be human immunodeficiency virus (HIV) positive are not eligible for
             the study given their potentially compromised immune systems and increased risk of
             treatment-related toxicity

          -  Advanced (T1N1-4/T2-3 N any) invasive cancer in the contralateral breast

          -  Any known history of cerebrovascular disease including TIA, stroke or subarachnoid
             hemorrhage

          -  Patients must not have a non-healing wound or fracture

          -  Patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal
             abscess within 6 months

          -  Patients must not have a bleeding diathesis, hereditary of acquired bleeding disorder
             or coagulopathy

          -  Patients on therapeutic doses of Coumadin or Lovenox are ineligible to participate in
             study

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study; core biopsy or other minor surgical procedure, for example
             placement of a vascular access device, are excluded from this requirement

          -  No known hypersensitivity to any component of bevacizumab