A Dose-Finding Study of Pertuzumab (Perjeta) in Combination With Trastuzumab (Herceptin) in Healthy Male Participants and Women With Early Breast Cancer (EBC)

Early Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02738970
• Other study ID #: BO30185
• Status: Completed
• Phase: Phase 1
• Start date: June 23, 2016
• Est. completion date: May 31, 2018

Study information

• Verified date: June 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: May 31, 2018
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Early Breast Cancer

Intervention

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

Locations

Country	Name	City	State
New Zealand	Auckland Clinical Studies	Auckland
New Zealand	Christchurch Clinical Studies Trust	Christchurch

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Secondary	Percentage of Participants with Adverse Events		Baseline up to approximately 24 months
Secondary	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)
Secondary	Percentage of Participants with ATAs to Trastuzumab		Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Secondary	Percentage of Participants with ATAs to rHuPH20		Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)