A Study of the Safety of Subcutaneously Administered Trastuzumab (Herceptin) in Participants With Early and Locally Advanced Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Doxorubicin; Docetaxel; Paclitaxel; Trastuzumab
Intervention description: Participants will receive doxorubicin in doses according to the locally-approved regimen q3w (1 cycle), for 4 cycles prior to initiation of trastuzumab treatment.; Participants will receive docetaxel in doses according to the locally-approved regimen q3w for 12 weeks, in combination with trastuzumab.; Participants will receive paclitaxel in doses according to the locally-approved regimen weekly for 12 weeks, in combination with trastuzumab.; Participants will receive trastuzumab 600 mg SC (vial or SID) q3w for 18 cycles.
Intervention MeSH terms: Paclitaxel; Docetaxel; Doxorubicin; Trastuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 240.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This non-randomized, multicenter, open-label study will assess the safety and efficacy of
      subcutaneously administered trastuzumab in participants with early and locally advanced
      HER2-positive breast cancer in two sequential cohorts. First 120 participants will be treated
      with subcutaneous (SC) trastuzumab 600 milligrams (mg) vial (Cohort A) and the subsequent 120
      participants will be treated with SC trastuzumab prefilled single use injection device (SID)
      (Cohort B). Participants from each cohort will receive neoadjuvant or adjuvant chemotherapy
      consisting of doxorubicin every 3 weeks (q3w) (1 cycle) for 4 cycles followed by paclitaxel
      weekly or docetaxel every 3 weeks (q3w) in combination with SC trastuzumab (600 mg) q3w for 4
      cycles and a further 14 cycles of SC trastuzumab (600 mg) q3w alone. All participants will be
      followed up for 24 months after the last participant has received the last dose of study
      treatment, or earlier in case of withdrawal from the study, loss to follow-up or death.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast.
             Stage of disease: T1-4 (T describes size of tumour from 1 to 4), N0-3 (N describes
             nearby lymph nodes), M0 (M describes distant metastasis)

          -  HER2-positive disease immunohistochemistry (IHC) 3+ or in situ hybridization (ISH)
             positive

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Left ventricular ejection fraction (LVEF) of greater than or equal to (>=) 55 percent
             (%) measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan
             prior to first dose of trastuzumab SC

          -  Intact skin at site of SC injection on the thigh

        Exclusion Criteria:

          -  History of other malignancy, except for participants with curatively treated carcinoma
             in situ of the cervix or basal cell carcinoma and participants with other curatively
             treated malignancies, other than breast cancer, who have been disease-free for at
             least 5 years

          -  Severe dyspnea at rest or requiring supplementary oxygen therapy

          -  Concurrent serious diseases that may interfere with planned treatment, including
             severe pulmonary conditions/illness

          -  Serious cardiac illness or medical conditions that would preclude the use of
             trastuzumab, specifically: history of documented congestive heart failure (CHF),
             high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically
             significant valvular disease, evidence of transmural infarction on electrocardiogram
             (ECG), diagnosed poorly controlled hypertension

          -  Known infection with human immunodeficiency virus (HIV), active hepatitis B virus
             (HBV) or hepatitis C virus (HCV)

          -  Pregnant or lactating women

          -  Concurrent enrolment in another clinical trial using an investigational anti-cancer
             treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy,
             within 28 days prior to the first dose of study treatment

          -  Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of
             Herceptin including hyaluronidase, or the adhesive of the SC device (for Cohort B), or
             a history of severe allergic or immunological reactions, for example, difficulty to
             control asthma

          -  Inadequate bone marrow, hepatic or renal function

          -  Hormonal treatment concomitant with chemotherapy (allowed in adjuvant phase with
             adjuvant trastuzumab SC)

          -  Pre-existing motor or sensory neuropathy of Grade greater than (>) 1

          -  Synchronous bilateral invasive breast cancer