A Study Evaluating Pertuzumab (Perjeta) Combined With Trastuzumab (Herceptin) and Standard Anthracycline-based Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: 5-Fluorouracil; Cyclophosphamide; Docetaxel; Doxorubicin; Epirubicin; Paclitaxel; Pertuzumab; Trastuzumab
Intervention description: Participants will receive 5-fluorouracil 500 mg/m^2 IV on Day 1 of each cycle q3w.; Participants will receive cyclophosphamide 600 milligrams per square meter (mg/m^2) intravenous (IV) given on Day 1 of each cycle q2w.; Participants will receive docetaxel at a starting dose of 75 mg/m^2 IV for the first cycle and the dose may be escalated to 100 mg/m^2 for subsequent cycles q3w.; Participants will receive doxorubicin 60 mg/m^2 IV on Day 1 of each cycle q2w.; Participants will receive epirubicin 100 mg/m^2 IV on Day 1 of each cycle q3w.; Participants will receive paclitaxel 80 mg/m^2 IV given weekly.; Participants will receive pertuzumab at a loading dose of 840 milligrams (mg) IV loading dose, then 420 mg IV q3w.; Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) IV, then 6 mg/kg IV q3w.
Intervention MeSH terms: Paclitaxel; Docetaxel; Cyclophosphamide; Doxorubicin; Fluorouracil; Trastuzumab; Epirubicin; Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 401.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This multicenter, non-randomized, open-label, phase 2 study is designed to evaluate the
      safety and efficacy of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and
      anthracycline-based chemotherapy as neoadjuvant treatment in participants with HER2-positive
      locally advanced, inflammatory, or early-stage breast cancer. Each investigator will choose a
      treatment regimen (A or B) for all of their participants to follow. Treatment regimen A (for
      Cohort A) will include dose-dense doxorubicin and cyclophosphamide (ddAC), followed by
      paclitaxel, with pertuzumab and trastuzumab given from the start of paclitaxel. Treatment
      regimen B (for Cohort B) will include 5-fluorouracil, epirubicin, and cyclophosphamide (FEC),
      followed by docetaxel, with pertuzumab and trastuzumab given from the start of docetaxel.
      Participants in both cohorts will subsequently undergo surgical treatment and then resume
      pertuzumab and trastuzumab treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female participants with locally advanced, inflammatory, or early-stage,
             unilateral, and histologically confirmed invasive breast cancer. Participants with
             inflammatory breast cancer must be able to have a core needle biopsy

          -  Primary tumor greater than (>) 2 centimeters (cm) in diameter, or > 5 millimeters (mm)
             in diameter and node-positive

          -  HER2-positive breast cancer confirmed by a central laboratory

          -  Availability of tumor tissue specimen

          -  Baseline LVEF greater than or equal to (>/=) 55%

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
             (</=) 1

          -  At least 4 weeks since major unrelated surgery, with full recovery

          -  Women of childbearing potential and male participants with partners of childbearing
             potential must agree to use a "highly effective" non-hormonal form of contraception or
             two "effective" forms of non-hormonal contraception by the patient and/or partner.
             Contraception must continue for the duration of study treatment and for at least 7
             months after the last dose of study treatment

        Exclusion Criteria:

          -  Metastatic disease (Stage IV) or bilateral breast cancer

          -  Participants who have had an incisional biopsy of the primary tumor or the primary
             tumor excised

          -  Prior breast or non-breast malignancy within 5 years prior to study entry, except for
             carcinoma in situ and basal cell and squamous cell carcinoma of the skin. Participants
             with malignancies occurring more than 5 years prior to study entry are permitted if
             curatively treated

          -  Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted
             agents, and antitumor vaccines) for cancer, or radiation therapy for cancer

          -  Participants with a past history of ductal carcinoma in situ (DCIS) or lobular
             carcinoma in situ (LCIS) are not allowed to enter the study if they have received any
             systemic therapy for its treatment or radiation therapy to the ipsilateral breast
             (they are allowed to enter the study if treated with surgery alone)

          -  High-risk participants who have received chemopreventive drugs in the past are not
             allowed to enter the study

          -  Inadequate bone marrow, renal, or liver function

          -  History or evidence of cardiovascular condition

          -  Dyspnea at rest or other diseases that require continuous oxygen therapy

          -  Severe, uncontrolled systemic disease

          -  Participants with poorly controlled diabetes or with evidence of clinically
             significant diabetic vascular complications

          -  Pregnancy or breast-feeding women

          -  Participants who received any investigational treatment within 4 weeks of study start

          -  Participants with known infection with human immunodeficiency virus (HIV), hepatitis B
             virus, or hepatitis C virus

          -  Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone
             or equivalent [excluding inhaled steroids])

          -  Known hypersensitivity to any of the study drugs or excipients