Breast CancerPhase 1NCT00800436
A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females
A Phase 1 study testing Herceptin in people with Breast Cancer, run by Hoffmann-La Roche at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Herceptin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Nov 2008to Oct 2009
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
About this study
Official title: An Open-Label, Two-Part, Multi-Centre, Trastuzumab Dose-Finding Study in Healthy Male Volunteers and HER2 Positive Female Patients
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.
- Conditions
- Breast Cancer
- Being tested
- Herceptin
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HerceptinDrug
Also called Trastuzumab
Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Cohort 1 | Experimental | Healthy male participants will receive Herceptin 6 mg/kg IV on Day 1. Receives: Drug: Herceptin |
| Part 1: Cohort 2 | Experimental | Female participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1. Receives: Drug: Herceptin |
| Part 1: Cohort 3 | Experimental | Healthy male participants will receive Herceptin 6 mg/kg SC on Day 1. Receives: Drug: Herceptin |
| Part 1: Cohort 4 | Experimental | Healthy male participants will receive Herceptin 10 mg/kg SC on Day 1. Receives: Drug: Herceptin |
| Part 1: Cohort 5 | Experimental | Healthy male participants will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohorts 1, 2, 3, and 4. Receives: Drug: Herceptin |
| Part 2: Cohort A | Experimental | Female participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1. Receives: Drug: Herceptin |
| Part 2: Cohort B | Experimental | Female participants with HER2-positive breast cancer will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohort A. Receives: Drug: Herceptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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 outcomes (4)
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).
Measured: Day 22
Maximum Observed Serum Concentration of Trastuzumab (Cmax)
Cmax of trastuzumab was derived across all post-dose PK collections and expressed in μg/mL.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00800436
- Sponsor's protocol ID
- BP22023
- Status last verified
- Oct 2016
- First submitted
- 1 Dec 2008
- Last updated
- 16 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 23436264
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Two-Part, Multi-Centre, Trastuzumab Dose-Finding Study in Healthy Male Volunteers and HER2 Positive Female Patients
- ClinicalTrials.gov ID
- NCT00800436
- Acronym / sponsor ID
- BP22023
- Conditions
- Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 2 Dec 2008 (estimated)
- Results
- Posted 16 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part 1: Cohort 1 | Experimental | Drug: HerceptinHealthy male participants will receive Herceptin 6 mg/kg IV on Day 1. |
| Part 1: Cohort 2 | Experimental | Drug: HerceptinFemale participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1. |
| Part 1: Cohort 3 | Experimental | Drug: HerceptinHealthy male participants will receive Herceptin 6 mg/kg SC on Day 1. |
| Part 1: Cohort 4 | Experimental | Drug: HerceptinHealthy male participants will receive Herceptin 10 mg/kg SC on Day 1. |
| Part 1: Cohort 5 | Experimental | Drug: HerceptinHealthy male participants will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohorts 1, 2, 3, and 4. |
| Part 2: Cohort A | Experimental | Drug: HerceptinFemale participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1. |
| Part 2: Cohort B | Experimental | Drug: HerceptinFemale participants with HER2-positive breast cancer will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohort A. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Healthy Participants (Part 1 only)
- HER2-Positive Females (Parts 1 and 2)
Key exclusion criteria (10 listed)
- Healthy Participants (Part 1 only)
- HER2-Positive Females (Parts 1 and 2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HerceptinAlso: TrastuzumabHerceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1. | Drug | Part 1: Cohort 1, Part 1: Cohort 2, Part 1: Cohort 3, Part 1: Cohort 4, Part 1: Cohort 5, Part 2: Cohort A, Part 2: Cohort B |
Primary outcome
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).
4 secondary outcomes
Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab
Time frame: Day 22
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23436264Wynne 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Herceptin in people with Breast Cancer, run by Hoffmann-La Roche at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in New Zealand, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00800436, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2016.