Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer
Condition: HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Breast Adenocarcinoma; Inflammatory Breast Carcinoma
MeSH terms: Breast Neoplasms; Inflammatory Breast Neoplasms
Intervention: pertuzumab; trastuzumab; paclitaxel albumin-stabilized nanoparticle formulation; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Optional correlative studies
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Trastuzumab; Pertuzumab; Antibodies; Immunoglobulins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: Female
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pertuzumab, trastuzumab, and paclitaxel
      albumin-stabilized nanoparticle formulation work in treating patients with human epidermal
      growth factor receptor (HER) 2-positive stage II-IV breast cancer. Monoclonal antibodies,
      such as pertuzumab and trastuzumab, 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. Drugs used in chemotherapy, such as paclitaxel
      albumin-stabilized nanoparticle formulation, work in different ways to kill tumor cells or
      stop them from growing. Giving pertuzumab and trastuzumab together with paclitaxel
      albumin-stabilized nanoparticle formulation may be a better way to block tumor growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be diagnosed with metastatic cytologically or histologically confirmed
             adenocarcinoma of the breast with HER2 over-expression or with newly diagnosed locally
             advanced (including inflammatory) breast cancer (LABC) with stage II-III disease;
             patients with metastatic (stage IV) disease (MBC) must have measurable lesions

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control or abstinence) prior to study entry and
             for six months following duration of study participation; should a woman become
             pregnant or suspect that she is pregnant while participating on the trial, she should
             inform her treating physician immediately

          -  Tumor positive or negative for expression of hormone receptors (< 1% or > 1%) and
             overexpressing HER2 by immunohistochemistry (IHC) (3+), or, HER2-amplified by
             fluorescence in situ hybridization (FISH) or by alternative gene testing

          -  For patients with LABC, no prior therapy is allowed

          -  For patients with MBC, prior adjuvant chemotherapy and trastuzumab more than or equal
             to 12 months prior to enrollment are allowed

          -  No prior chemotherapy or trastuzumab for treatment of metastatic breast cancer

          -  Left ventricular ejection fraction (LVEF) >= 50% (determined by echocardiogram or
             multigated acquisition scan) within 42 days of treatment

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Hemoglobin >= 9 g/dl

          -  Leukocytes >= 3.0 x 10^9/L

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Total bilirubin =< 1.3 mg/dl (institutional upper limit of normal)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2 x institutional upper limit of normal

          -  Creatinine within normal institutional limits or creatinine clearance > 50 mL/min/1.73
             m^2 for patients with creatinine levels above institutional normal (using
             Cockcroft-Gault formula)

          -  All radiology studies (study requiring staging) must be performed within 35 days prior
             to the start of therapy

          -  No serious medical conditions such as myocardial infarction within 6 months prior to
             entry, congestive heart failure, unstable ventricular arrhythmia, uncontrolled
             hypertension, uncontrolled diabetes mellitus, uncontrolled psychotic disorders,
             serious infections, active peptic ulcer disease, psychiatric illness, or any other
             medical conditions that might be aggravated by treatment or limit compliance

          -  Currently, no active second malignancy other than non-melanoma skin cancer; note:
             patients are not considered to have a "current active" malignancy if they have
             completed anti-cancer therapy and are considered by their physicians to have a less
             than 30% chance of relapse

          -  All patients must have the ability to understand and the willingness to sign an
             informed consent

          -  Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at
             screening for patients of child-bearing potential

          -  No prior therapies (except for anti-estrogen therapy) are allowed for the treatment of
             the newly diagnosed metastatic breast cancer; patients are allowed to have had prior
             chemotherapy for breast cancer in the adjuvant setting for at least 12 months prior to
             enrollment into this study; patients with a prior diagnosis of malignancy treated >= 5
             years ago are eligible, provided that they have not received prior nab-paclitaxel as
             part of their prior treatment regimen, and that they meet all eligibility criteria

        Exclusion Criteria:

          -  Known active hepatitis B or C

          -  Known active human immunodeficiency virus (HIV)

          -  Prior breast cancer or other invasive malignancy treated within 5 years

          -  Pregnancy

          -  Neuropathy > grade 1

          -  Any other intercurrent medical/psychological problem deemed exclusionary by the
             treating physician or investigators/principal investigator (PI)

          -  Cumulative dose of doxorubicin or equivalent of > 360 mg/m^2 during prior adjuvant
             therapy

          -  LVEF < 50% during previous trastuzumab therapy

          -  Central nervous system metastases

          -  Another malignancy excluding basal cell skin cancer

          -  Pregnant women

          -  Subjects will be excluded who, in the opinion of the investigator, may not be able to
             comply with the safety monitoring requirements of the study