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NCT Number: NCT02738970

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

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.

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Key information

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Auckland Clinical Studies, Auckland, New Zealand

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Trastuzumab

Drug

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

Other names: Herceptin, RO0452317

Pertuzumab

Drug

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.

Other names: Perjeta, RO4368451

Primary outcomes

  1. Area Under the Concentration from Time Zero to Time Infinity (AUC0-inf) of Pertuzumab SC

    Time frame: 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)

  2. Maximum Serum Concentration (Cmax) of Pertuzumab SC

    Time frame: 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)

  3. Time to Reach Cmax (Tmax) of Pertuzumab SC

    Time frame: 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)

  4. Minimum Serum Concentration (Cmin) of Pertuzumab SC

    Time frame: 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)

  5. AUC0-inf of Pertuzumab IV

    Time frame: 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)

  6. Cmax of Pertuzumab IV

    Time frame: 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)

  7. Tmax of Pertuzumab IV

    Time frame: 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)

  8. Cmin of Pertuzumab IV

    Time frame: 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

  1. Percentage of Participants with Adverse Events

    Time frame: Baseline up to approximately 24 months

  2. Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Pertuzumab

    Time frame: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)

  3. Percentage of Participants with ATAs to Trastuzumab

    Time frame: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)

  4. Percentage of Participants with ATAs to rHuPH20

    Time frame: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Apr 14, 2016
Registry last updated
Jun 12, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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