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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)

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02738970
Collaborator
(none)
88
Enrollment
2
Locations
11
Arms
23.2
Actual Duration (Months)
44
Patients Per Site
1.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
88 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 23, 2016
Actual Primary Completion Date :
May 31, 2018
Actual Study Completion Date :
May 31, 2018

Arms and Interventions

Arm Intervention/Treatment
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.

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 Names:
  • Perjeta, RO4368451

    		•
    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.

    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 Names:
  • Perjeta, RO4368451

    		•
    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.

    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 Names:
  • Perjeta, RO4368451

    		•
    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.

    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 Names:
  • Perjeta, RO4368451

    		•
    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.

    Drug: Trastuzumab
    Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
    Other Names:
  • Herceptin, RO0452317

    		•
    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.

    Drug: Trastuzumab
    Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
    Other Names:
  • 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 Names:
  • Perjeta, RO4368451

    		•
    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.

    Drug: Trastuzumab
    Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
    Other Names:
  • 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 Names:
  • Perjeta, RO4368451

    		•
    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.

    Drug: Trastuzumab
    Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
    Other Names:
  • 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 Names:
  • Perjeta, RO4368451

    		•
    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.

    Drug: Trastuzumab
    Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
    Other Names:
  • 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 Names:
  • Perjeta, RO4368451

    		•
    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.

    Drug: Trastuzumab
    Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
    Other Names:
  • 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 Names:
  • Perjeta, RO4368451

    		•
    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.

    Drug: Trastuzumab
    Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.
    Other Names:
  • 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 Names:
  • Perjeta, RO4368451

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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)]

    2. 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)]

    3. 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)]

    4. 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)]

    5. 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)]

    6. 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)]

    7. 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)]

    8. 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 Outcome Measures

    1. Percentage of Participants with Adverse Events [Baseline up to approximately 24 months]

    2. 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)]

    3. Percentage of Participants with ATAs to Trastuzumab [Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)]

    4. Percentage of Participants with ATAs to rHuPH20 [Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Auckland Clinical Studies Auckland New Zealand 1142
    2 Christchurch Clinical Studies Trust Christchurch New Zealand 8011

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02738970
    Other Study ID Numbers:
    • BO30185
    First Posted:
    Apr 14, 2016
    Last Update Posted:
    Jun 12, 2018
    Last Verified:
    Jun 1, 2018
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Breast Neoplasms
    Trastuzumab
    Pertuzumab

    Study Results

    No Results Posted as of Jun 12, 2018