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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
Scientific title
An Open-Label, Two-Part, Multi-Centre, Trastuzumab Dose-Finding Study in Healthy Male Volunteers and HER2 Positive Female Patients
Secondary ID [1] 0 0
BP22023
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab
Timepoint [1] 0 0
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)
Secondary outcome [1] 0 0
Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab
Timepoint [1] 0 0
Day 22
Secondary outcome [2] 0 0
Maximum Observed Serum Concentration of Trastuzumab (Cmax)
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Time to Maximum Serum Concentration (Tmax) of Trastuzumab
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Terminal Elimination Half-Life (T1/2) of Trastuzumab
Timepoint [4] 0 0
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)

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%
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2009
Sample size
Target
Accrual to date
Final
66
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- East Bentleigh
Recruitment postcode(s) [1] 0 0
VIC 3165 - East Bentleigh
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch
Country [2] 0 0
New Zealand
State/province [2] 0 0
Grafton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00800436
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00800436