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

Roche

Status and phase: Completed; Phase 1

Conditions: Breast Cancer

Treatments: Drug: Herceptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00800436

BP22023

Details and patient eligibility

About

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.

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

66 participants in 7 patient groups

Part 1: Cohort 1

Experimental group

Description:

Healthy male participants will receive Herceptin 6 mg/kg IV on Day 1.

Treatment:

Drug: Herceptin

Part 1: Cohort 2

Experimental group

Description:

Female participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1.

Treatment:

Drug: Herceptin

Part 1: Cohort 3

Experimental group

Description:

Healthy male participants will receive Herceptin 6 mg/kg SC on Day 1.

Treatment:

Drug: Herceptin

Part 1: Cohort 4

Experimental group

Description:

Healthy male participants will receive Herceptin 10 mg/kg SC on Day 1.

Treatment:

Drug: Herceptin

Part 1: Cohort 5

Experimental group

Description:

Healthy male participants will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohorts 1, 2, 3, and 4.

Treatment:

Drug: Herceptin

Part 2: Cohort A

Experimental group

Description:

Female participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1.

Treatment:

Drug: Herceptin

Part 2: Cohort B

Experimental group

Description:

Female participants with HER2-positive breast cancer will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohort A.

Treatment:

Drug: Herceptin