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

• ClinicalTrials.gov Identifier: NCT02738970
• Recruitment Status: Completed
• First Posted: April 14, 2016
• Last Update Posted: June 12, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 29, 2016
• First Posted Date: April 14, 2016
• Last Update Posted Date: June 12, 2018
• Actual Study Start Date: June 23, 2016
• Actual Primary Completion Date: May 31, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2017)

• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]

Original Primary Outcome Measures (submitted: April 11, 2016)

• SC Perjeta Loading Dosage (in Milligrams) that Results in Comparable Exposure to IV Perjeta (When SC Perjeta is Mixed with Herceptin SC and Given as a Single Injection) as Assessed by a Compilation of PK Parameters (AUC, Cmax, Tmax, Ctrough) [ Time Frame: PK sampling pre-dose (0 hours) and post-dose (1.5, 3, 6, 8, 12 hours) on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 35, 43, 85; and at follow-up (up to approximately 11 months overall) ]
• SC Perjeta Maintenance Dosage (in Milligrams) that Results in Comparable Exposure to IV Perjeta (When SC Perjeta is Mixed with Herceptin SC and Given as a Single Injection) as Assessed by a Compilation of PK Parameters (AUC, Cmax, Tmax, Ctrough) [ Time Frame: PK sampling pre-dose (0 hours) and post-dose (1.5, 3, 6, 8, 12 hours) on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 35, 43, 85; and at follow-up (up to approximately 11 months overall) ]
• SC Perjeta Loading Dosage (in Milligrams) that Results in Comparable Exposure to IV Perjeta (When SC Perjeta is Given as Single-Agent Injection) as Assessed by a Compilation of PK Parameters (AUC, Cmax, Tmax, Ctrough) [ Time Frame: PK sampling pre-dose (0 hours) and post-dose (1.5, 3, 6, 8, 12 hours) on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 35, 43, 85; and at follow-up (up to approximately 11 months overall) ]
• SC Perjeta Maintenance Dosage (in Milligrams) that Results in Comparable Exposure to IV Perjeta (When SC Perjeta is Given as Single-Agent Injection) as Assessed by a Compilation of PK Parameters (AUC, Cmax, Tmax, Ctrough) [ Time Frame: PK sampling pre-dose (0 hours) and post-dose (1.5, 3, 6, 8, 12 hours) on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 35, 43, 85; and at follow-up (up to approximately 11 months overall) ]

• Change History: Complete list of historical versions of study NCT02738970 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 10, 2017)

• Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 24 months ]
• 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) ]
• 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) ]
• 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) ]

Original Secondary Outcome Measures (submitted: April 11, 2016)

• Percentage of Participants with Adverse Events [ Time Frame: Continuously from Screening to 7 months post-dose (up to approximately 11 months overall) ]
• Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Any Study Drug [ Time Frame: Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 11 months overall) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.
  Other Name: Herceptin, RO0452317
• Drug: 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.
  Other Name: Perjeta, RO4368451

Study Arms

• Active Comparator: Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV
  Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 420 mg IV.
  Intervention: Drug: Pertuzumab
• Experimental: Part 1-Cohort 2: Pertuzumab 400 mg SC
  Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 400 mg SC.
  Intervention: Drug: Pertuzumab
• Experimental: Part 1-Cohort 3: Pertuzumab 600 mg SC
  Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 600 mg SC.
  Intervention: Drug: Pertuzumab
• Experimental: Part 1-Cohort 4: Pertuzumab 1200 mg SC
  Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 1200 mg SC.
  Intervention: Drug: Pertuzumab
• Active Comparator: Part 1-Cohort 5: Trastuzumab 600 mg SC
  Part 1 includes healthy male participants. Participants will receive a single injection of trastuzumab 600 mg SC.
  Intervention: Drug: Trastuzumab
• Experimental: Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC
  Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 400 mg and trastuzumab 600 mg SC.
  Interventions:

  • Drug: Trastuzumab
  • Drug: Pertuzumab
• Experimental: Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC
  Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC.
  Interventions:

  • Drug: Trastuzumab
  • Drug: Pertuzumab
• Experimental: Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC
  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.
  Interventions:

  • Drug: Trastuzumab
  • Drug: Pertuzumab
• Experimental: Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC
  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.
  Interventions:

  • Drug: Trastuzumab
  • Drug: Pertuzumab
• Experimental: Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC
  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.
  Interventions:

  • Drug: Trastuzumab
  • Drug: Pertuzumab
• Experimental: Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC
  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.
  Interventions:

  • Drug: Trastuzumab
  • Drug: Pertuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 11, 2016): 88
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 31, 2018
• Actual Primary Completion Date: May 31, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: New Zealand

Administrative Information

• NCT Number: NCT02738970
• Other Study ID Numbers: BO30185
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: June 2018