Last updated: 11/03/2018 19:03:13

PGx419: Pharmacogenetic Evaluation of Decrease in Left Ventricular Ejection Fraction (LVEF) in Lapatinib Treated Metastatic Breast Cancer (MBC) Subjects

GSK study ID
116294
See study documents
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: PGx419: Pharmacogenetic Evaluation of Decrease in Left Ventricular Ejection Fraction (LVEF) in Lapatinib Treated Metastatic Breast Cancer (MBC) Subjects
Trial description: Pre-clinical studies have shown that ablation of HER2 (ErbB2) pathway signalling may be involved in cardiomyocyte survival and cardiac function. Trastuzumab, a humanized monoclonal antibody directed against HER2, is associated with cardiac dysfunction and may compound the effects of previous anthracycline-induced cardiac damage. Trastuzumab and anthracyclines may have different mechanisms of cardiotoxicity. Most patients with HER2-positive breast cancer receive anthracyclines followed by trastuzumab and could therefore be at increased risk of cardiac toxicity. On the basis of experience with trastuzumab, cardiac function was prospectively assessed in clinical studies of lapatinib treated subjects as lapatinib also targets HER2. Cardiotoxicity manifests as symptomatic or asymptomatic decrease in left ventricular ejection fraction (LVEF) in MBC patients during lapatinib treatment, albeit at an incidence lower than trastuzumab (1.5-3% vs. 7%). A functional SNP in HER2 (I655V; rs1801200) has been reported to be associated with trastuzumab induced cardiotoxicity in small samples (n=57-73) of breast cancer patients (Milano et al., ASCO 2005; Beauclair et al., 2007; Diorio et al., ASCO 2012). Thus, genetics may be used to elucidate the mechanism of this adverse event and to predict patients at risk of experiencing a decrease in LVEF. Therefore, an exploratory pharmacogenetic (PGx) analysis was undertaken in subjects from 10 metastatic breast cancer (MBC) clinical trials to investigate whether germline genetic variants associate with LVEF decrease observed during lapatinib treatment.
Primary purpose:
Not applicable
Trial design:
Not applicable
Masking:
Not applicable
Allocation:
Not applicable
Primary outcomes:

In a meta-analysis of the metastatic breast cancer subjects from 10 different lapatinib studies, identify germline genetic variants (candidate variants or variants from whole genome scan) that may associate with LVEF decrease in lapatinib treated subject

Timeframe: N/A

Secondary outcomes:
Not applicable
Interventions:
  • Drug: lapatinib
    • Enrollment:
    1
    Primary completion date:
    Not applicable
    Observational study model:
    Case-Control
    Time perspective:
    Retrospective
    Clinical publications:
    Not applicable
    Medical condition
    Neoplasms, Breast
    Product
    lapatinib
    Collaborators
    Not applicable
    Study date(s)
    November 2011 to April 2012
    Type
    Observational
    Phase
    Not applicable

    Participation criteria

    Sex
    Female
    Age
    Not applicable
    Accepts healthy volunteers
    none
    • Patients that provided written informed consent for PGx research when they enrolled in the clinical study EGF10023, EGF20009, EGF103009, EGF100151, EGF30001, EGF104900, EGF30008, EGF104383, EGF105084, and VEG20007 and did not withdraw consent prior to PGx experiment
    • Patients that provided a blood sample for genotyping
    • Patients that did not provide written informed consent for PGx research when they enrolled in the clinical study EGF10023, EGF20009, EGF103009, EGF100151, EGF30001, EGF104900, EGF30008, EGF104383, EGF105084, and VEG20007, or withdrew their PGx consent prior to genotyping being conducted
    • Patients that did not provide any or an adequate blood sample for genotyping
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Patients that provided written informed consent for PGx research when they enrolled in the clinical study EGF10023, EGF20009, EGF103009, EGF100151, EGF30001, EGF104900, EGF30008, EGF104383, EGF105084, and VEG20007 and did not withdraw consent prior to PGx experiment
    • Patients that provided a blood sample for genotyping
    • Patients that successfully genotyped for GWAS and candidate genes under study and passed quality control measures
    • Patients whose valid clinical data available
    Exclusion criteria:
    • Patients that did not provide written informed consent for PGx research when they enrolled in the clinical study EGF10023, EGF20009, EGF103009, EGF100151, EGF30001, EGF104900, EGF30008, EGF104383, EGF105084, and VEG20007, or withdrew their PGx consent prior to genotyping being conducted
    • Patients that did not provide any or an adequate blood sample for genotyping
    • Patients that failed genotyping
    • Patients that did not have valid clinical data available

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    Study complete
    Actual primary completion date
    Not applicable
    Actual study completion date
    2012-23-04

    Plain language summaries

    Not applicable. GSK’s transparency policy provides for Plain Language Summaries for Interventional studies.

    Additional information about the trial

    Not applicable
    Participate in clinical trial
    Access to clinical trial data by researchers
    Visit website