A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females

• Status: Completed
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Trastuzumab

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