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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00800436
First Posted: December 2, 2008
Last Update Posted: December 16, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
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.

Condition Intervention Phase
Breast Cancer Drug: Herceptin Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Two-Part, Multi-Centre, Trastuzumab Dose-Finding Study in Healthy Male Volunteers and HER2 Positive Female Patients

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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).

  • 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.

  • 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.

  • 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.


Enrollment: 66
Study Start Date: November 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Cohort 1
Healthy male participants will receive Herceptin 6 mg/kg IV on Day 1.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Name: Trastuzumab
Experimental: Part 1: Cohort 2
Female participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Name: Trastuzumab
Experimental: Part 1: Cohort 3
Healthy male participants will receive Herceptin 6 mg/kg SC on Day 1.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Name: Trastuzumab
Experimental: Part 1: Cohort 4
Healthy male participants will receive Herceptin 10 mg/kg SC on Day 1.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Name: Trastuzumab
Experimental: Part 1: Cohort 5
Healthy male participants will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohorts 1, 2, 3, and 4.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Name: Trastuzumab
Experimental: Part 2: Cohort A
Female participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Name: Trastuzumab
Experimental: Part 2: Cohort B
Female participants with HER2-positive breast cancer will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohort A.
Drug: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
Other Name: Trastuzumab

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00800436


Locations
Australia
East Bentleigh, Australia, VIC 3165
New Zealand
Christchurch, New Zealand, 8011
Grafton, New Zealand, 1150
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00800436     History of Changes
Other Study ID Numbers: BP22023
First Submitted: December 1, 2008
First Posted: December 2, 2008
Results First Submitted: October 24, 2016
Results First Posted: December 16, 2016
Last Update Posted: December 16, 2016
Last Verified: October 2016

Additional relevant MeSH terms:
Trastuzumab
Antineoplastic Agents