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

NCT ID: NCT02738970

Last Updated: 2018-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-23
• Study Completion Date: 2018-05-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: 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.

Interventions

Trastuzumab

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Herceptin, RO0452317; Perjeta, RO4368451

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Auckland Clinical Studies

Auckland, , New Zealand

Christchurch Clinical Studies Trust

Christchurch, , New Zealand

Countries

New Zealand

References

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.

Reference Type: DERIVED

PMID: 30570763 (View on PubMed)

Other Identifiers

BO30185

Identifier Type: -

Identifier Source: org_study_id