A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females
Condition: Breast Cancer
Intervention: Herceptin
Intervention description: Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Intervention MeSH terms: Trastuzumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This two-part study is designed to select the subcutaneous (SC) dose of Herceptin that
      results in comparable exposure to intravenous (IV) Herceptin in healthy male participants and
      in HER2-positive female participants. The study will also assess the safety and tolerability
      of the SC and IV formulations. In Part 1 of the study, four cohorts will be treated with a
      single dose of Herceptin as follows: Cohort 1 (6 milligrams per kilogram [mg/kg] IV in
      healthy male participants); Cohort 2 (6 mg/kg IV in HER2-positive female participants);
      Cohort 3 (6 mg/kg SC in healthy male participants); Cohort 4 (10 mg/kg SC in healthy male
      participants). An additional cohort of healthy volunteers (Cohort 5) will be opened if both
      SC dose levels from Cohorts 3 and 4 result in Herceptin exposures different from the target
      concentration produced by a single IV dose, or if the variability in pharmacokinetic (PK)
      parameter values cannot be used to define the target SC dose level. In Part 2 of the study,
      HER2-positive female participants will receive a single dose of SC Herceptin at the dose
      level defined in Part 1. Participants from Part 1 are eligible to enter Part 2 provided they
      receive the second (Part 2) study dose of Herceptin a minimum of 22 days after their first
      (Part 1) dose.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy Participants (Part 1 only)

               -  Males 18 to 45 to years of age

               -  Baseline left ventricular ejection fraction (LVEF) greater than (>) 60 percent
                  (%)

          -  HER2-Positive Females (Parts 1 and 2)

               -  Females greater than or equal to (≥) 18 years of age

               -  Eastern Cooperative Oncology Group (ECOG) performance status of 0

               -  Previous non-metastatic operable primary invasive HER2-positive breast cancer

               -  Baseline LVEF >55%

        Exclusion Criteria:

          -  Healthy Participants (Part 1 only)

               -  Clinically significant abnormalities in laboratory test results or
                  electrocardiogram

               -  History of significant allergies, gastrointestinal, renal, hepatic,
                  cardiovascular, or pulmonary disease

               -  History of hypersensitivity or allergic reaction, spontaneous or following drug
                  administration

               -  History of cardiac conditions

          -  HER2-Positive Females (Parts 1 and 2)

               -  Metastatic disease

               -  Concurrent other malignancy requiring therapy of any modality which may interfere
                  with PK investigations or result in unexpected toxicity

               -  Use of Herceptin in previous 5 months

               -  Serious cardiac illness