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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/NCT02738970




Registration number
NCT02738970
Ethics application status
Date submitted
29/03/2016
Date registered
14/04/2016
Date last updated
12/06/2018

Titles & IDs
Public title
A Dose-Finding Study of Pertuzumab (Perjeta) in Combination With Trastuzumab (Herceptin) in Healthy Male Participants and Women With Early Breast Cancer (EBC)
Scientific 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
Secondary ID [1] 0 0
BO30185
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Pertuzumab

Active Comparator: Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV - Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 420 mg IV.

Experimental: Part 1-Cohort 2: Pertuzumab 400 mg SC - Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 400 mg SC.

Experimental: Part 1-Cohort 3: Pertuzumab 600 mg SC - Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 600 mg SC.

Experimental: Part 1-Cohort 4: Pertuzumab 1200 mg SC - Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 1200 mg SC.

Active Comparator: Part 1-Cohort 5: Trastuzumab 600 mg SC - Part 1 includes healthy male participants. Participants will receive a single injection of trastuzumab 600 mg SC.

Experimental: Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC - Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 400 mg and trastuzumab 600 mg SC.

Experimental: Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC - Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC.

Experimental: Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC - 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.

Experimental: Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC - 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.

Experimental: Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC - 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.

Experimental: Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC - 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.


Treatment: Drugs: Trastuzumab
Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.

Treatment: Drugs: Pertuzumab
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Concentration from Time Zero to Time Infinity (AUC0-inf) of Pertuzumab SC
Timepoint [1] 0 0
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)
Primary outcome [2] 0 0
Maximum Serum Concentration (Cmax) of Pertuzumab SC
Timepoint [2] 0 0
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)
Primary outcome [3] 0 0
Time to Reach Cmax (Tmax) of Pertuzumab SC
Timepoint [3] 0 0
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)
Primary outcome [4] 0 0
Minimum Serum Concentration (Cmin) of Pertuzumab SC
Timepoint [4] 0 0
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)
Primary outcome [5] 0 0
AUC0-inf of Pertuzumab IV
Timepoint [5] 0 0
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)
Primary outcome [6] 0 0
Cmax of Pertuzumab IV
Timepoint [6] 0 0
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)
Primary outcome [7] 0 0
Tmax of Pertuzumab IV
Timepoint [7] 0 0
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)
Primary outcome [8] 0 0
Cmin of Pertuzumab IV
Timepoint [8] 0 0
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 outcome [1] 0 0
Percentage of Participants with Adverse Events
Timepoint [1] 0 0
Baseline up to approximately 24 months
Secondary outcome [2] 0 0
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Pertuzumab
Timepoint [2] 0 0
Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Secondary outcome [3] 0 0
Percentage of Participants with ATAs to Trastuzumab
Timepoint [3] 0 0
Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Secondary outcome [4] 0 0
Percentage of Participants with ATAs to rHuPH20
Timepoint [4] 0 0
Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)

Eligibility
Key inclusion criteria
- 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

- 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
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- 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

- 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

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
23/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/05/2018
Sample size
Target
Accrual to date
Final
88
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch

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

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02738970
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/NCT02738970