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

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

Tracking Information
First Submitted Date  ICMJE March 29, 2016
First Posted Date  ICMJE April 14, 2016
Last Update Posted Date June 12, 2018
Actual Study Start Date  ICMJE June 23, 2016
Actual Primary Completion Date May 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE
 (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  ICMJE
 (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  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Early Breast Cancer
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 11, 2016)
88
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 31, 2018
Actual Primary Completion Date May 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02738970
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP