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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: trastuzumab emtansine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild hepatic dysfunction<br> | Drug: trastuzumab emtansine<br>* Multiple intravenous doses<br>|
| Experimental: Moderate hepatic dysfunction<br> | Drug: trastuzumab emtansine<br>* Multiple intravenous doses<br>|
| Experimental: Normal hepatic function<br> | Drug: trastuzumab emtansine<br>* Multiple intravenous doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |