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.
Conditions
Interventions
Trade Name: Tyverb
Product Name: Lapatinib
Product Code: GW572016
Pharmaceutical Form: Film-coated tablet
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 lapatinibtreated 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
Exclusion criteria
Exclusion criteria: N/A
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Not applicable;Timepoint(s) of evaluation of this end point: Once all blood samples have been collected, they will be shipped to Quest for storage then to an expert academic research group in the UK.;Main Objective: The overall objective is to determine key events involved in sensitisation and lapatinibinduced hepatotoxicity in selected subjects. The following objectives outline key workstreams for investigation. 1) Characterisation of lapatinib-specific ex vivo stimulation and proliferation of peripheral blood mononuclear cells (PBMCs) by comparison of subjects who experienced lapatinib-induced liver injury (cases) with HLA and geographic matched, lapatinib-treated, but tolerant controls (treatment controls) and with HLA and geographic matched placebo-treated, normal liver chemistry controls (disease controls). 2) Define the phenotype (CD4/CD8 expression) and function (cytokine release, helper or cytotoxic phenotype) of lapatinib-specific T cells. Please refer to the protocol for further deatils P7.;Primary end point(s): Lymphocyte proliferation by [3H]thymidine incorporation. Cytokine release profiles of activated T cell subsets by EliSpot and specific ELISA assays of supernatant of cultured cells. CD4/CD8 expression in T cell subsets by flow cytometry to determine whether functional activation of T cells is restricted to the CD4 or CD8 compartments. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
Argentina, Denmark, Spain, United States
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed