Clinical trial NCT01513083: A Study of Trastuzumab Emtansine in Patients With HER2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-01-20
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics: Area under the concentration-time curve
timeFrame: Multiple sampling pre- and up to 21 days post-dose Cycles 1-3
Secondary outcomes:
measure: Safety: Incidence of adverse events in patients with mild or moderate hepatic impairment as compared to patients with normal hepatic function
timeFrame: approximately 2 years
Other outcomes:
Locations:
city: Fort Myers
country: United States
state: Florida
city: Detroit
country: United States
state: Michigan
city: Portland
country: United States
state: Oregon
city: Nashville
country: United States
state: Tennessee
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Marseille
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Catanzaro
country: Italy
state: Calabria
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Barcelona
country: Spain
city: Madrid
country: Spain
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: