A Study of Trastuzumab Emtansine in Patients With HER2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function

A Phase I, Open Label, Parallel Group, Pharmacokinetic Study of Trastuzumab Emtansine in Patients With HER2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function

This open-label, parallel group study will evaluate the pharmacokinetics and safety of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer and normal or reduced hepatic function. Patients will receive trastuzumab emtansine intravenously on Day 1 of each 3-week cycle. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: trastuzumab emtansine

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
    • Toronto, Ontario, Canada, M5G 2M9
• France
  • Marseille, France, 13273
  • Paris, France, 75231
  • Toulouse, France, 31059
• Italy
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
• Spain
  • Barcelona, Spain, 08003
  • Madrid, Spain, 28007
• United States
  • Florida
    • Fort Myers, Florida, United States, 33905
  • Michigan
    • Detroit, Michigan, United States, 48201
  • Oregon
    • Portland, Oregon, United States, 97239
  • Tennessee
    • Nashville, Tennessee, United States, 37203

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically or cytologically documented invasive metastatic breast cancer
• Human epidermal growth factor receptor 2 (HER2) -positive disease
• Adequate bone marrow and organ function (other than hepatic dysfunction allowed by protocol)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Left ventricular ejection fraction >/=50%
• Normal hepatic function, or mild to moderate hepatic impairment (Child-Pugh Class A or B)

Exclusion Criteria:

• History of Grade >/=3 infusion reaction, hypersensitivity reaction, or pneumonitis in response to trastuzumab
• Investigational therapy or any other anticancer therapy </=28 days before first study treatment
• Previous treatment with trastuzumab emtansine
• Brain metastases that are untreated or symptomatic or require therapy to control symptoms or any radiation, surgery or other therapy to control symptoms from brain metastases within 1 month of the first study treatment
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those mentioned above
• Current peripheral neuropathy of Grade >/=2
• Child-Pugh Class C hepatic impairment
• Encephalopathy >/= Grade 2
• For patients with normal hepatic function: history of drug or alcohol addiction or history of hepatitis B and/or hepatitis C
• Active hepatitis A, B and/or C
• Current unstable ventricular arrhythmia requiring treatment
• History of symptomatic CHF (NYHA Classes II-IV)
• History of myocardial infarction or unstable angina within 6 months of enrollment
• History of a decrease in LVEF to<40% or symptomatic CHF with previous trastuzumab treatment
• Pregnant or lactating women
• Known HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal hepatic function	Drug: trastuzumab emtansine; Multiple intravenous doses
Experimental: Mild hepatic dysfunction	Drug: trastuzumab emtansine; Multiple intravenous doses
Experimental: Moderate hepatic dysfunction	Drug: trastuzumab emtansine; Multiple intravenous doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Area under the concentration-time curve	Multiple sampling pre- and up to 21 days post-dose Cycles 1-3

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events in patients with mild or moderate hepatic impairment as compared to patients with normal hepatic function	approximately 2 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: January 16, 2012
• First Submitted That Met QC Criteria: January 16, 2012
• First Posted (Estimate): January 20, 2012

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: BO25499; 2011-004591-10 (EudraCT Number)