A Study to Assess Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab and Vinorelbine in Participants With Metastatic or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Pertuzumab; Trastuzumab; Vinorelbine
Intervention description: Loading dose of 840 mg on Day 1 of first 21-day cycle, followed by 420 mg on Day 1 of each subsequent cycle.; Loading dose of 8 mg/kg on Day 1 of first 21-day cycle, followed by 6 mg/kg on Day 1 or 2 of each subsequent cycle.; A dose of 25 mg/m^2 followed by 30-35 mg/m^2 on Days 2 and 9 of the first 21-day cycle and on Days 1 and 8 (or Days 2 and 9) of each subsequent cycle.
Intervention MeSH terms: Trastuzumab; Pertuzumab; Vinorelbine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 213.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This two-cohort, open-label, multicenter, phase 2 study will assess the safety and efficacy
      of pertuzumab given in combination with trastuzumab (Herceptin) and vinorelbine in first line
      participants with metastatic or locally advanced HER2-positive breast cancer. Participants
      will receive pertuzumab and trastuzumab administered sequentially as separate intravenous
      (IV) infusions (followed by vinorelbine) and conventional sequential administration of
      pertuzumab and trastuzumab in separate infusion bags, followed by vinorelbine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed and documented adenocarcinoma of the breast
             with metastatic or locally advanced disease not amenable to curative resection

          -  HER2-positive as assessed by local laboratory on primary or metastatic tumor

          -  At least one measurable lesion and/or non-measurable disease evaluable according to
             RECIST v1.1 criteria

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Left ventricular ejection fraction (LVEF) of at least 55%

          -  Life expectancy of at least 12 weeks

        Exclusion Criteria:

          -  Previous systemic non-hormonal anti-cancer therapy in the metastatic or locally
             advanced breast cancer setting

          -  Previous approved or investigative anti-HER2 agents in any breast cancer treatment
             setting, except trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting

          -  Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or
             neoadjuvant setting

          -  Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal
             treatment to recurrent disease of less than 6 months

          -  History of persistent Grade 2 or higher (National Cancer Institute Common Terminology
             Criteria [NCI-CTC], Version 4.0) hematological toxicity resulting from previous
             adjuvant or neoadjuvant therapy

          -  Radiographic evidence of central nervous system metastases that are not well
             controlled with local therapy (irradiation or surgery)

          -  Current peripheral neuropathy of NCI-CTC, version 4.0 Grade 3 or greater

          -  History of other malignancy within the last 5 years, except for carcinoma in situ of
             the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, or cancers with a
             similar curative outcome as those mentioned above

          -  Serious uncontrolled concomitant disease that would contraindicate the use of any of
             the investigational drugs used in this study or would put the participants at high
             risk for treatment-related complications

          -  Inadequate hematologic, liver, or renal function

          -  Uncontrolled hypertension or clinically significant cardiovascular disease

          -  Hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection

          -  Current chronic daily treatment with corticosteroids (>/= 10 mg/day methylprednisolone
             or equivalent), excluding inhaled steroids