Clinical trial NCT02738970: A Dose-Finding Study of Pertuzumab (Perjeta) in Combination With Trastuzumab (Herceptin) in Healthy Male Participants and Women With Early Breast Cancer (EBC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Early Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Concentration from Time Zero to Time Infinity (AUC0-inf) of Pertuzumab SC
timeFrame: 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)
measure: Maximum Serum Concentration (Cmax) of Pertuzumab SC
timeFrame: 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)
measure: Time to Reach Cmax (Tmax) of Pertuzumab SC
timeFrame: 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)
measure: Minimum Serum Concentration (Cmin) of Pertuzumab SC
timeFrame: 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)
measure: AUC0-inf of Pertuzumab IV
timeFrame: 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)
measure: Cmax of Pertuzumab IV
timeFrame: 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)
measure: Tmax of Pertuzumab IV
timeFrame: 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)
measure: Cmin of Pertuzumab IV
timeFrame: 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:
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline up to approximately 24 months
measure: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Pertuzumab
timeFrame: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
measure: Percentage of Participants with ATAs to Trastuzumab
timeFrame: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
measure: Percentage of Participants with ATAs to rHuPH20
timeFrame: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.