Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

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
Early Breast Cancer Drug: Trastuzumab Drug: Pertuzumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : June 23, 2016
Actual Primary Completion Date : May 31, 2018
Actual Study Completion Date : May 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 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

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 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

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 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

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 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

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 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

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 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




Primary Outcome Measures :
  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 Outcome Measures :
  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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02738970


Locations
Layout table for location information
New Zealand
Auckland Clinical Studies
Auckland, New Zealand, 1142
Christchurch Clinical Studies Trust
Christchurch, New Zealand, 8011
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche

Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02738970     History of Changes
Other Study ID Numbers: BO30185
First Posted: April 14, 2016    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Pertuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents