A Study of a Combination of Trastuzumab and Capecitabine With or Without Pertuzumab in Patients With HER2-positive Metastatic Breast Cancer (PHEREXA)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Capecitabine; Capecitabine; Pertuzumab; Trastuzumab
Intervention description: 1000 mg/m2 po twice daily for 14 days every 3 weeks; 1250 mg/m2 po twice daily for 14 days every 3 weeks; 840 mg iv loading, then 420 mg iv every 3 weeks; 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks
Intervention MeSH terms: Capecitabine; Trastuzumab; Pertuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 452.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized, two-arm study evaluated the efficacy and safety of a combination of
      trastuzumab and capecitabine with or without pertuzumab in patients with human epidermal
      growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study population
      consisted of female patients, whose disease had progressed during or following previous
      trastuzumab therapy for metastatic disease. All patients in Arm A and Arm B received
      trastuzumab (8 mg/kg iv as loading dose and then 6 mg/kg iv every 3 weeks thereafter) and
      capecitabine oral twice daily for 14 days every 3 weeks (1250 mg/m2 twice daily in Arm A and
      1000 mg/m2 twice daily in Arm B). In addition, patients in Arm B received pertuzumab (840 mg
      iv as loading dose and then 420 mg iv thereafter) every 3 weeks. Study treatment continued
      until disease progression or unacceptable toxicity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult female patients >/=18 years of age

          -  Metastatic HER2 positive breast cancer

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Disease progression during or following trastuzumab-based therapy for 1st line
             metastatic breast cancer (trastuzumab must have been part of the last prior treatment
             regimen)

          -  Prior treatment with taxane-containing regimen

          -  Left ventricular ejection fraction (LVEF) >/=50 percent

          -  For women of childbearing potential agreement to use highly effective non-hormonal
             form of contraception or two effective forms of non-hormonal contraception by patient
             and/or partner. Contraception must continue for duration of study treatment and for at
             least 6 months after last dose of study drug treatment

        Exclusion Criteria:

          -  Prior treatment with pertuzumab or capecitabine

          -  Concurrent treatment with other experimental drug

          -  Concurrent immunotherapy or anticancer hormonal therapy

          -  Serious concurrent disease (e.g. active infection, uncontrolled hypertension,
             cardiovascular disease)

          -  Central nervous system (CNS) metastases, which are not well controlled

          -  History of exposure to anthracycline cumulative dose equivalent to 360mg/m2

          -  History of congestive heart failure of any New York Heart Association criteria, or
             serious cardiac arrhythmia requiring treatment

          -  History of myocardial infarction within 6 months prior to randomization

          -  History of LVEF decline to below 50% during or after prior trastuzumab therapy or
             other cardiac toxicity during previous trastuzumab treatment that necessitated
             discontinuation of trastuzumab

          -  History of another cancer which could affect compliance or result interpretation

          -  Inadequate organ function

          -  Pregnant or breastfeeding women

          -  life expectancy < 12 weeks