A Dose-Finding Study of Pertuzumab (Perjeta) in Combination With Trastuzumab (Herceptin) in Healthy Male Participants and Women With Early Breast Cancer (EBC)
- Registration Number
- NCT02738970
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 88
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
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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
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC Trastuzumab Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC. Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV Pertuzumab Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 420 mg IV. Part 1-Cohort 5: Trastuzumab 600 mg SC Trastuzumab Part 1 includes healthy male participants. Participants will receive a single injection of trastuzumab 600 mg SC. Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC Trastuzumab Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 400 mg and trastuzumab 600 mg SC. Part 1-Cohort 2: Pertuzumab 400 mg SC Pertuzumab Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 400 mg SC. Part 1-Cohort 3: Pertuzumab 600 mg SC Pertuzumab Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 600 mg SC. Part 1-Cohort 4: Pertuzumab 1200 mg SC Pertuzumab Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 1200 mg SC. Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC Pertuzumab Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 400 mg and trastuzumab 600 mg SC. Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC Pertuzumab Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC. Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC Trastuzumab 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. Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC Pertuzumab 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. Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC Pertuzumab 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. Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC Trastuzumab 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. Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC Trastuzumab 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. Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC Pertuzumab 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. Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC Pertuzumab 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. Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC Trastuzumab 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.
- Primary Outcome Measures
Name Time Method Area Under the Concentration from Time Zero to Time Infinity (AUC0-inf) of Pertuzumab SC 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 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 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) Cmin of Pertuzumab IV 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) Minimum Serum Concentration (Cmin) of Pertuzumab SC 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 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 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 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 Measures
Name Time Method Percentage of Participants with Adverse Events Baseline up to approximately 24 months Percentage of Participants with ATAs to rHuPH20 Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall) Percentage of Participants with ATAs to Trastuzumab Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall) Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Pertuzumab Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Trial Locations
- Locations (2)
Christchurch Clinical Studies Trust
🇳🇿Christchurch, New Zealand
Auckland Clinical Studies
🇳🇿Auckland, New Zealand