Early Breast Cancer
Conditions
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.
Interventions
DRUGTrastuzumab
Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
DRUGPertuzumab
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) |
| 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) |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| 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 ATAs to rHuPH20 | Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall) |
| Percentage of Participants with Adverse Events | Baseline up to approximately 24 months |
Countries
New Zealand
Outcome results
None listed