Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer
Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer
The purpose of this study is to see if a combination of drugs can help to treat this type of
 cancer. One drug is a chemotherapy agent called paclitaxel (Taxol®). Paclitaxel will be given
 every week through the vein. Although the weekly schedule of paclitaxel is not included in
 the label, the schedule and dose of weekly paclitaxel have been studied and have been proven
 to be more effective than an old standard schedule. The other two work against HER2. One is
 called trastuzumab (Herceptin®) and it is commonly given to women with early HER2 positive
 breast cancer or with advanced HER2 positive breast cancer that has spread to other parts of
 the body. Trastuzumab will be given through the vein every 3 weeks (or every week at the
 doctor's discretion). The third drug, pertuzumab, is an investigational drug. It has not been
 approved by the Food and Drug Administration. It has been given in studies to over 800
 people. It has been effective in treating HER2 positive breast cancer. Pertuzumab will be
 given every 3 weeks through the vein. This study is looking at the effectiveness of these
 three drugs together.
Inclusion Criteria:

 -  Age ≥18

 -  Stage IV HER2 (+) breast cancer.

 -  Histologically documented HER2 (+) breast cancer as defined as IHC 3+ or FISH
 amplification of ≥ 2.0 of primary or metastatic site; results from the local lab are
 acceptable. (Optional tumor sample collection from primary or metastatic site may be
 obtained for HER2 testing at MSKCC).

 -  ECOG performance 0 -1 (Appendix A)

 -  0-1 prior treatment in the metastatic setting (ie: hormone, chemotherapy, biologic,
 targeted agents). Prior anthracycline, paclitaxel, and trastuzumab in the adjuvant
 setting are allowed. If the patient has one trastuzumab-based treatment in the
 metastatic setting and is given a break (even intermittently) from the partner drug
 given with trastuzumab and is continued on trastuzumab alone, this would still be
 considered as one treatment. For example, if the patient was given paclitaxel +
 trastuzumab and was later continued on trastuzumab alone or then restarted on
 paclitaxel + trastuzumab (at the physician's discretion for any reason), the regimen
 paclitaxel + trastuzumab followed by trastuzumab alone (or followed by paclitaxel +
 trastuzumab again) may be considered as one treatment.

 -  Measurable or non-measurable disease. Measurable lesions are defined as those that can
 be measured accurately in at least one diameter, that is 20 mm using conventional
 imaging techniques (including incremental CT) or 10 mm using spiral CT equipment and a
 lymph node 15 mm along the short axis. Non-measurable lesions are all other lesions,
 including small lesions (longest diameter <10mm pathological a lymph nodes with 10 to
 less than 15mm along the short axis, bony metastases, leptomeningeal disease, ascites,
 pleural/pericardial effusions, inflammatory breast cancer, lymphangitis
 carcinomatosis, and heavily calcified and cystic/necrotic lesions.

 -  LVEF ≥ 50%

 -  Hematologic parameters: white blood cell (WBC) count of ≥ 3000/ul, absolute neutrophil
 count (ANC) ≥1500/ul, platelets ≥ 100,000/ul, hemoglobin ≥ 10.0 g/dl

 -  Non-hematologic parameters: bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 2.5 x upper limit of
 normal (ULN), alkaline phosphatase ≤ 5 x ULN.

 -  Creatinine ≤ 1.5 mg/dl

 -  Patients with stable and treated brain lesions of a duration of ≥ 2 months may be
 enrolled.

 Exclusion Criteria:

 -  History of prior cardiac morbidities within 12 months (unstable angina, myocardial
 infarction, CHF, uncontrolled ventricular arrhythmias)

 -  Prior pertuzumab

 -  History of prior ≥ G 3 hypersensitivity (HSR) or any toxicity to trastuzumab that
 warranted permanent cessation of this antibody

 -  History of prior ≥ G 3 HSR or any toxicity to paclitaxel warranted permanent cessation
 of this chemotherapy

 -  > G 2 peripheral neuropathy

 -  Patients with a history of chronic hepatitis B or C should be excluded from the study
 as paclitaxel is potentially hepatotoxic

 -  Pregnant patients