Investigation of immune mechanisms relating to lapatinib associated hepatotoxicity (liver toxicity)
- Conditions
- The subjects participated in the EGF105485 study, a randomized, placebo-controlled study of lapatinib in HER2-positive early-stage breast cancer. During participation in this study, subjects had blood test results that may be suggestive of liver damage.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-000572-15-ES
- Lead Sponsor
- GlaxoSmithKline, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 75
Note that treatment and disease controls will only be collected if their respective, matched case is able to consent and provide a blood sample.
The four groups of subjects will be selected as follows: i) lapatinib-treated subjects who had a previously reported and documented hepatic serious adverse event (cases), ii) selected lapatinib treated subjects who did not experience liver adverse events, with normal liver chemistries at baseline and throughout treatment (treatment controls) and iii) placebo treated subjects who had normal liver chemistries at baseline and throughout treatment (disease controls). Subjects for the two control groups will be matched with the casesbased on their HLA-DQA1*02:01/DRB1*07:01 allele carriage, ethnicity, study site (where possible) and country.
In addition, HLA-DRB1*07:01 and ?DQA1*02:01 alleles are inherited together in 99.8% of the study population and genetic investigation has not determined which of the two alleles is causative for hepatotoxicity. However, three EGF105485 (TEACH) subjects have been identified with a rare mismatch of inheriting only one of these highly correlated alleles: HLA-DRB1*07:01 (1 subject, lapatinib treatment) or HLADQA1* 02:01 (2 subjects, lapatinib or placebo treatment). These three subjects were characterised as controls and reside in North America. Whole blood samples will be collected to enable comparison of T cell activation following lapatinib challenge ex vivo.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19
N/A
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method