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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00800436
Registration number
NCT00800436
Ethics application status
Date submitted
1/12/2008
Date registered
2/12/2008
Date last updated
16/12/2016
Titles & IDs
Public title
A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females
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Scientific title
An Open-Label, Two-Part, Multi-Centre, Trastuzumab Dose-Finding Study in Healthy Male Volunteers and HER2 Positive Female Patients
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Secondary ID [1]
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BP22023
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Breast Cancer
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Herceptin
Experimental: Part 1: Cohort 1 - Healthy male participants will receive Herceptin 6 mg/kg IV on Day 1.
Experimental: Part 1: Cohort 2 - Female participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1.
Experimental: Part 1: Cohort 3 - Healthy male participants will receive Herceptin 6 mg/kg SC on Day 1.
Experimental: Part 1: Cohort 4 - Healthy male participants will receive Herceptin 10 mg/kg SC on Day 1.
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.
Experimental: Part 2: Cohort A - Female participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1.
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.
Treatment: Drugs: Herceptin
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab
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Assessment method [1]
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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).
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Timepoint [1]
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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)
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Secondary outcome [1]
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Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab
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Assessment method [1]
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CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (µg/mL).
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Timepoint [1]
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Day 22
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Secondary outcome [2]
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Maximum Observed Serum Concentration of Trastuzumab (Cmax)
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Assessment method [2]
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Cmax of trastuzumab was derived across all post-dose PK collections and expressed in µg/mL.
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Timepoint [2]
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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)
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Secondary outcome [3]
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Time to Maximum Serum Concentration (Tmax) of Trastuzumab
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Assessment method [3]
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Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.
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Timepoint [3]
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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)
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Secondary outcome [4]
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Terminal Elimination Half-Life (T1/2) of Trastuzumab
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Assessment method [4]
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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.
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Timepoint [4]
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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)
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Eligibility
Key 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%
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/11/2008
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/10/2009
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Sample size
Target
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Accrual to date
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Final
66
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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- East Bentleigh
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Recruitment postcode(s) [1]
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VIC 3165 - East Bentleigh
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Recruitment outside Australia
Country [1]
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New Zealand
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State/province [1]
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Christchurch
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Country [2]
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New Zealand
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State/province [2]
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Grafton
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief 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.
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Trial website
https://clinicaltrials.gov/study/NCT00800436
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Trial related presentations / publications
Wynne C, Harvey V, Schwabe C, Waaka D, McIntyre C, Bittner B. Comparison of subcutaneous and intravenous administration of trastuzumab: a phase I/Ib trial in healthy male volunteers and patients with HER2-positive breast cancer. J Clin Pharmacol. 2013 Feb;53(2):192-201. doi: 10.1177/0091270012436560.
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Public notes
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Contacts
Principal investigator
Name
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Clinical Trials
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Address
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Hoffmann-La Roche
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT00800436
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