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

NCT02738970 | Completed Phase 1

• 1 other identifier: BO30185
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 2

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.

Conditions

Early Breast Cancer

Outcome Measures

Primary Outcomes (8)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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 Outcomes (4)

• Percentage of Participants with Adverse Events

  Baseline up to approximately 24 months

• 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)

• Percentage of Participants with ATAs to Trastuzumab

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

• Percentage of Participants with ATAs to rHuPH20

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

Study Arms (11)

Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV

ACTIVE COMPARATOR

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 420 mg IV.

Drug: Pertuzumab

Part 1-Cohort 2: Pertuzumab 400 mg SC

EXPERIMENTAL

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 400 mg SC.

Drug: Pertuzumab

Part 1-Cohort 3: Pertuzumab 600 mg SC

EXPERIMENTAL

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 600 mg SC.

Drug: Pertuzumab

Part 1-Cohort 4: Pertuzumab 1200 mg SC

EXPERIMENTAL

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 1200 mg SC.

Drug: Pertuzumab

Part 1-Cohort 5: Trastuzumab 600 mg SC

ACTIVE COMPARATOR

Part 1 includes healthy male participants. Participants will receive a single injection of trastuzumab 600 mg SC.

Drug: Trastuzumab

Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC

EXPERIMENTAL

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; Drug: Pertuzumab

Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC

EXPERIMENTAL

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; Drug: Pertuzumab

Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC

EXPERIMENTAL

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; Drug: Pertuzumab

Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC

EXPERIMENTAL

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; Drug: Pertuzumab

Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC

EXPERIMENTAL

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; Drug: Pertuzumab

Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC

EXPERIMENTAL

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; Drug: Pertuzumab

Interventions

Trastuzumab DRUG

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

Also known as: Herceptin, RO0452317

Part 1-Cohort 5: Trastuzumab 600 mg SC; Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC; Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC; Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC; Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC; Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC; Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC

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.

Also known as: Perjeta, RO4368451

Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV; Part 1-Cohort 2: Pertuzumab 400 mg SC; Part 1-Cohort 3: Pertuzumab 600 mg SC; Part 1-Cohort 4: Pertuzumab 1200 mg SC; Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC; Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC; Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC; Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC; Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC; Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Auckland Clinical Studies

Auckland, 1142, New Zealand

Location

Christchurch Clinical Studies Trust

Christchurch, 8011, New Zealand

Location

Related Publications (1)

• Kirschbrown WP, Wynne C, Kagedal M, Wada R, Li H, Wang B, Nijem I, Badovinac Crnjevic T, Gasser H, Heeson S, Eng-Wong J, Garg A. Development of a Subcutaneous Fixed-Dose Combination of Pertuzumab and Trastuzumab: Results From the Phase Ib Dose-Finding Study. J Clin Pharmacol. 2019 May;59(5):702-716. doi: 10.1002/jcph.1362. Epub 2018 Dec 19.

  PMID: 30570763 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 14, 2016
• Study Start: June 23, 2016
• Primary Completion: May 31, 2018
• Study Completion: May 31, 2018
• Last Updated: June 12, 2018

Record last verified: 2018-06

Locations

NZ (2)