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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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 - 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).
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 - CDay22 of trastuzumab was derived from the single PK collection on Day 22 and expressed in micrograms per milliliter (µg/mL).
Timepoint [1] 0 0
Day 22
Secondary outcome [2] 0 0
Maximum Observed Serum Concentration of Trastuzumab (Cmax) - Cmax of trastuzumab was derived across all post-dose PK collections and expressed in µg/mL.
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 - Tmax of trastuzumab was based on the Cmax derived across all post-dose PK collections and expressed in hours.
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 - 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.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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/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
Other publications