Breast Cancer
Conditions
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.
Interventions
DRUGtrastuzumab emtansine
Multiple intravenous doses
Sponsors
Hoffmann-La Roche
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Area under the concentration-time curve | Multiple sampling pre- and up to 21 days post-dose Cycles 1-3 |
Secondary
| 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 |
Countries
Canada, France, Italy, Spain, United States
Outcome results
None listed