A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females

NCT00800436 | Completed Phase 1 Results

• 1 other identifier: BP22023
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 3

Brief Summary

This two-part study is designed to select the subcutaneous (SC) dose of Herceptin that results in comparable exposure to intravenous (IV) Herceptin in healthy male participants and in HER2-positive female participants. The study will also assess the safety and tolerability of the SC and IV formulations. In Part 1 of the study, four cohorts will be treated with a single dose of Herceptin as follows: Cohort 1 (6 milligrams per kilogram \[mg/kg\] IV in healthy male participants); Cohort 2 (6 mg/kg IV in HER2-positive female participants); Cohort 3 (6 mg/kg SC in healthy male participants); Cohort 4 (10 mg/kg SC in healthy male participants). An additional cohort of healthy volunteers (Cohort 5) will be opened if both SC dose levels from Cohorts 3 and 4 result in Herceptin exposures different from the target concentration produced by a single IV dose, or if the variability in pharmacokinetic (PK) parameter values cannot be used to define the target SC dose level. In Part 2 of the study, HER2-positive female participants will receive a single dose of SC Herceptin at the dose level defined in Part 1. Participants from Part 1 are eligible to enter Part 2 provided they receive the second (Part 2) study dose of Herceptin a minimum of 22 days after their first (Part 1) dose.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Trastuzumab

  AUCinf represents the area under the concentration-time curve of trastuzumab in serum over the time interval from 0 extrapolated to infinity. Values for AUCinf of trastuzumab were derived by non-compartmental analysis across all pharmacokinetic (PK) collections and expressed in days by micrograms per milliliter (days•μg/mL).

  Predose (0 hours) and postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

Secondary Outcomes (4)

• Trough Serum Concentration on Day 22 (CDay22) of Trastuzumab

  Day 22

• Maximum Observed Serum Concentration of Trastuzumab (Cmax)

  Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

• Time to Maximum Serum Concentration (Tmax) of Trastuzumab

  Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

• Terminal Elimination Half-Life (T1/2) of Trastuzumab

  Postdose from start of 1.5-hour infusion (1.5 and 3 hours for IV) (6, 8, 12 hours for SC) on Day 1; on Days 2, 3, 5, 8, 15, 22, 43, 85; additionally on Day 10 for SC and Day 35 for IV; and 5 months postdose (up to 5 months overall)

Study Arms (7)

Part 1: Cohort 1

EXPERIMENTAL

Healthy male participants will receive Herceptin 6 mg/kg IV on Day 1.

Drug: Herceptin

Part 1: Cohort 2

EXPERIMENTAL

Female participants with HER2-positive breast cancer will receive Herceptin 6 mg/kg IV on Day 1.

Drug: Herceptin

Part 1: Cohort 3

EXPERIMENTAL

Healthy male participants will receive Herceptin 6 mg/kg SC on Day 1.

Drug: Herceptin

Part 1: Cohort 4

EXPERIMENTAL

Healthy male participants will receive Herceptin 10 mg/kg SC on Day 1.

Drug: Herceptin

Part 1: Cohort 5

EXPERIMENTAL

Healthy male participants will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohorts 1, 2, 3, and 4.

Drug: Herceptin

Part 2: Cohort A

EXPERIMENTAL

Female participants with HER2-positive breast cancer will receive Herceptin SC at the dose level determined in Part 1.

Drug: Herceptin

Part 2: Cohort B

EXPERIMENTAL

Female participants with HER2-positive breast cancer will receive Herceptin SC at an adjusted dose level based on preliminary PK analysis of Cohort A.

Drug: Herceptin

Interventions

Herceptin DRUG

Herceptin will be administered IV or SC at various dosages (depending upon the cohort to which the participant is assigned) on Day 1.

Also known as: Trastuzumab

Part 1: Cohort 1; Part 1: Cohort 2; Part 1: Cohort 3; Part 1: Cohort 4; Part 1: Cohort 5; Part 2: Cohort A; Part 2: Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Participants (Part 1 only)
• Males 18 to 45 to years of age
• Baseline left ventricular ejection fraction (LVEF) greater than (\>) 60 percent (%)
• HER2-Positive Females (Parts 1 and 2)
• Females greater than or equal to (≥) 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0
• Previous non-metastatic operable primary invasive HER2-positive breast cancer
• Baseline LVEF \>55%

You may not qualify if:

• Healthy Participants (Part 1 only)
• Clinically significant abnormalities in laboratory test results or electrocardiogram
• History of significant allergies, gastrointestinal, renal, hepatic, cardiovascular, or pulmonary disease
• History of hypersensitivity or allergic reaction, spontaneous or following drug administration
• History of cardiac conditions
• HER2-Positive Females (Parts 1 and 2)
• Metastatic disease
• Concurrent other malignancy requiring therapy of any modality which may interfere with PK investigations or result in unexpected toxicity
• Use of Herceptin in previous 5 months
• Serious cardiac illness

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

Unknown Facility

East Bentleigh, VIC 3165, Australia

Location

Unknown Facility

Christchurch, 8011, New Zealand

Location

Unknown Facility

Grafton, 1150, New Zealand

Location

Related Publications (1)

• Wynne C, Harvey V, Schwabe C, Waaka D, McIntyre C, Bittner B. Comparison of subcutaneous and intravenous administration of trastuzumab: a phase I/Ib trial in healthy male volunteers and patients with HER2-positive breast cancer. J Clin Pharmacol. 2013 Feb;53(2):192-201. doi: 10.1177/0091270012436560.

  PMID: 23436264 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: December 1, 2008
• First Posted: December 2, 2008
• Study Start: November 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: December 16, 2016
• Results First Posted: December 16, 2016

Record last verified: 2016-10

Locations

AU (1); NZ (2)