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

Phase 1

Completed

• Conditions: Breast Cancer
• Interventions: Drug: trastuzumab emtansine

• Registration Number: NCT01513083
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-01-16
• Study First Submitted QC: 2012-01-16
• Study First Posted: 2012-01-20
• Study Start: 2012-02
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mild hepatic dysfunction	trastuzumab emtansine	-
Moderate hepatic dysfunction	trastuzumab emtansine	-
Normal hepatic function	trastuzumab emtansine	-

Primary Outcome Measures

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

Secondary Outcome Measures

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