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NCT Number: NCT00800436

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

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

East Bentleigh, Australia

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Herceptin

Drug

Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.

Other names: Trastuzumab

Primary outcomes

  1. Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab

    Time frame: Predose (0 hours) and postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).

Secondary outcomes

  1. Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab

    Time frame: Day 22

    CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (μg/mL).

  2. Maximum Observed Serum Concentration of Trastuzumab (Cmax)

    Time frame: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    Cmax of trastuzumab was derived across all post-dose PK collections and expressed in μg/mL.

  3. Time to Maximum Serum Concentration (Tmax) of Trastuzumab

    Time frame: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.

  4. Terminal Elimination Half-Life (T1/2) of Trastuzumab

    Time frame: Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

    T1/2 of trastuzumab was measured as the time required for trastuzumab concentration to decrease by one-half. T1/2 was derived across all PK collections and expressed in hours.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

An Open-Label, Two-Part, Multi-Centre, Trastuzumab Dose-Finding Study in Healthy Male Volunteers and HER2 Positive Female Patients

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Dec 2, 2008
Registry last updated
Dec 16, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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