Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: pertuzumab in combination with trastuzumab and paclitaxel
Intervention description: The regimen will consist of paclitaxel (80 mg/m2) weekly + trastuzumab every 3 weeks (8 mg/kg loading dose → 6 mg/kg every 3 weeks) + pertuzumab every 3 weeks (840 mg as a loading dose → 420 mg), all given intravenously (IV). Patients may be given trastuzumab weekly in lieu of every 3 weeks (4 mg/kg loading dose → 2 mg/kg every 3 weeks). Patients will be on treatment until progression of disease.
Intervention MeSH terms: Paclitaxel; Trastuzumab; Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MAB 2C4 (PERTUZUMAB); MAB HER 2 (HERCEPTIN) (TRASTUZUMAB); TAXOL (PACLITAXEL); 10-142; Stage IV HER2 (+) breast cancer

Summary:

      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.
    

Eligibility criteria:

        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