Early Breast CancerPhase 1NCT02738970
A Dose-Finding Study of Pertuzumab (Perjeta) in Combination With Trastuzumab (Herceptin) in Healthy Male Participants and Women With Early Breast Cancer (EBC)
A Phase 1 study testing Trastuzumab and Pertuzumab in people with Early Breast Cancer, run by Hoffmann-La Roche at 2 sites in New Zealand.
Trial summary
This study involves a two-part design. Part 1 is designed to determine the optimal dose of subcutaneous (SC) Perjeta, injected alone or mixed with Herceptin, that results in comparable exposure to intravenous (IV) Perjeta. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Early Breast Cancer
- What is being tested?
- Trastuzumab and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 2 sitesNew Zealand
- Study dates
- 23 Jun 2016to 31 May 2018
- Phase
- Phase 1
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 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Part 1: Healthy male volunteers 18 to 45 years of age
- Part 1: Left ventricular ejection fraction (LVEF) at least 55 percent (%)
- Part 1: Body mass index (BMI) 18 to 32 kilograms per meter-squared (kg/m^2)
- Part 1: Normal, intact skin without tattoos or lesions in the injection area
- Part 2: Females at least 18 years of age
- Part 2: Eastern Cooperative Oncology Group (ECOG) performance status of 0
Show all 9Show fewer
- Part 2: Previously treated, non-metastatic carcinoma of the breast
- Part 2: Baseline LVEF at least 55%
- Part 2: Negative pregnancy test and use of adequate contraceptive measures among women of childbearing potential
Who cannot join
- Part 1: Positive urine test for drugs of abuse
- Part 1: History of exposure or active viral infection of Hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
- Part 1: Cardiac disease including hypertension or hypotension
- Part 1: Lower extremity edema
- Part 1: Any clinically relevant history of systemic disease
- Part 1: History of breast cancer
Show all 16Show fewer
- Part 1: Chronic corticosteroid use
- Part 1: Receipt of IV antibiotics within 7 days prior to enrollment
- Part 2: Concurrent malignancy requiring therapy that may interfere with pharmacokinetic investigations, or history of other malignancy within 5 years prior to Screening
- Part 2: Significant cumulative exposure to anthracyclines
- Part 2: Serious cardiac disease including uncontrolled hypertension
- Part 2: Poor hematologic, renal, or hepatic function
- Part 2: Pregnant or lactating women
- Part 2: History of exposure or active viral infection of Hepatitis B, hepatitis C, or HIV
- Part 2: Chronic corticosteroid use
- Part 2: Receipt of IV antibiotics within 7 days prior to enrollment
Trial locations and contacts
2 sites in 1 country.
New Zealand2 sites
Auckland Clinical Studies
Auckland, 1142
Christchurch Clinical Studies Trust
Christchurch, 8011
About this study
Official title: A Phase I, Open-Label, Two-Part, Multicenter Perjeta® Subcutaneous Dose-Finding Study in Combination With Herceptin® in Healthy Male Volunteers and Female Patients With Early Breast Cancer
This study involves a two-part design. Part 1 is designed to determine the optimal dose of subcutaneous (SC) Perjeta, injected alone or mixed with Herceptin, that results in comparable exposure to intravenous (IV) Perjeta. Exposure between SC Perjeta and IV Perjeta will be compared using a compilation of pharmacokinetic (PK) parameters such as area under the concentration-time curve (AUC), maximum serum concentration (Cmax), time of maximum concentration (Tmax), and serum trough concentration (Ctrough). Part 2 is designed to confirm the dosing regimen in women with EBC on the basis of safety, tolerability, and PK assessments.
- Conditions
- Early Breast Cancer
- Being tested
- Trastuzumab, Pertuzumab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin, RO0452317
Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
PertuzumabDrug
Also called Perjeta, RO4368451
Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.
| Study group | Role | What they receive |
|---|---|---|
| Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV | Active comparator | Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 420 mg IV. Receives: Drug: Pertuzumab |
| Part 1-Cohort 2: Pertuzumab 400 mg SC | Experimental | Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 400 mg SC. Receives: Drug: Pertuzumab |
| Part 1-Cohort 3: Pertuzumab 600 mg SC | Experimental | Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 600 mg SC. Receives: Drug: Pertuzumab |
| Part 1-Cohort 4: Pertuzumab 1200 mg SC | Experimental | Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 1200 mg SC. Receives: Drug: Pertuzumab |
| Part 1-Cohort 5: Trastuzumab 600 mg SC | Active comparator | Part 1 includes healthy male participants. Participants will receive a single injection of trastuzumab 600 mg SC. Receives: Drug: Trastuzumab |
| Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC | Experimental | Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 400 mg and trastuzumab 600 mg SC. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
| Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC | Experimental | Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
| Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC | Experimental | Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC without recombinant human hyaluronidase (rHuPH20) excipient. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
| Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC | Experimental | Part 2 includes women with early breast cancer. Cohort A will be enrolled only if FDC of pertuzumab and trastuzumab is not feasible. Participants will receive pertuzumab and trastuzumab (600 mg) SC administered separately. The dose of pertuzumab will be identified during Part 1. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
| Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC | Experimental | Part 2 includes women with early breast cancer. Cohorts B and C will be enrolled if FDC of pertuzumab and trastuzumab is feasible. Participants will receive pertuzumab and trastuzumab (600 mg) SC; both agents administered in one injection (co-mixed). The dose of pertuzumab will be identified during Part 1. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
| Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC | Experimental | Part 2 includes women with early breast cancer. Cohorts B and C will be enrolled if FDC of pertuzumab and trastuzumab is feasible. Participants will receive pertuzumab and trastuzumab (600 mg) SC; both agents formulated together and administered in one injection (FDC). The dose of pertuzumab will be identified during Part 1. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Concentration from Time Zero to Time Infinity (AUC0-inf) of Pertuzumab SC
Measured: Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
Maximum Serum Concentration (Cmax) of Pertuzumab SC
Measured: Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
Time to Reach Cmax (Tmax) of Pertuzumab SC
Measured: Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
Minimum Serum Concentration (Cmin) of Pertuzumab SC
Measured: Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
AUC0-inf of Pertuzumab IV
Measured: Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)
Cmax of Pertuzumab IV
Measured: Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)
Tmax of Pertuzumab IV
Measured: Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)
Cmin of Pertuzumab IV
Measured: Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)
Secondary outcomes (4)
Percentage of Participants with Adverse Events
Measured: Baseline up to approximately 24 months
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Pertuzumab
Measured: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Percentage of Participants with ATAs to Trastuzumab
Measured: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Percentage of Participants with ATAs to rHuPH20
Measured: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2016 (estimated)
- Study start23 Jun 2016
- Primary completion31 May 2018
- Study completion31 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Early 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
- 88 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
- NCT02738970
- Sponsor's protocol ID
- BO30185
- Status last verified
- Jun 2018
- First submitted
- 29 Mar 2016
- Last updated
- 12 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kirschbrown WP, Wynne C, Kagedal M, Wada R, Li H, Wang B, Nijem I, Badovinac Crnjevic T, Gasser H, Heeson S, Eng-Wong J, Garg A. Development of a Subcutaneous Fixed-Dose Combination of Pertuzumab and Trastuzumab: Results From the Phase Ib Dose-Finding Study. J Clin Pharmacol. 2019 May;59(5):702-716. doi: 10.1002/jcph.1362. Epub 2018 Dec 19.
PubMed 30570763