Last updated: 02/04/2020 15:40:06

Exploratory PGx Analysis of ALT elevation in EGF105485

GSK study ID
117394
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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: Exploratory PGx Analysis of ALT elevation in EGF105485
Trial description: EGF105485, the TEACH study (Tykerb Evaluation After Chemotherapy), is a large, randomized, placebo-controlled study of adjuvant lapatinib in patients with early stage, HER2 over-expressing breast cancer. A previous, prospectively defined pharmacogenetic analysis (EGF114471) utilizing TEACH study data, has prospectively validated the associations of four major histocompatibility complex (MHC) region genetic variants with lapatinib-induced hepatotoxicity, including HLA-DRB1*07:01 and –DQA1*02:01.
This pharmacogenetic experiment was retrospectively designed to investigate the association of additional genetic variants with lapatinib-induced alanine aminotransferase (ALT) elevation and additional genetic markers that may refine the previously confirmed association with HLA-DRB1*07:01 and –DQA1*02:01 in the lapatinib-treated patients carrying these specified HLA risk variants. Statistical analysis of genetic data generated during EGF114471 along with clinical data collected in study EGF105485 was used to evaluate the associations between genetic variants (including candidate genes, Genome Wide Association Scan (GWAS), classical HLA alleles and amino acid residues) and ALT endpoints (including both continuous and case control status). For declaring experiment-wide statistical significance, bonferroni-threshold criteria 1x10-4 (0.05/500) and 5x10-8 (0.05/1,000,000) were applied to candidate gene and GWAS results, respectively.
Additional exploratory analyses were planned to further our knowledge about any genetic contribution to hepatobiliary adverse events in the lapatinib-treated patients by exploring other variant types and/or analysis methods and incorporating knowledge of tissue-relevant functional data to annotate SNPs.
Primary purpose:
Not applicable
Trial design:
Not applicable
Masking:
Not applicable
Allocation:
Not applicable
Primary outcomes:

Determine if genetic markers are associated with maximum on treatment ALT as a continuous endpoint or ‘strict’ ALT cases and controls as a binary endpoint.

Timeframe: N/A

Secondary outcomes:
Not applicable
Interventions:
  • Drug: lapatinib
    • Enrollment:
    0
    Primary completion date:
    2013-08-03
    Observational study model:
    Case-Control
    Time perspective:
    Retrospective
    Clinical publications:
    Not applicable
    Medical condition
    Neoplasms, Breast
    Product
    lapatinib
    Collaborators
    Not applicable
    Study date(s)
    December 2012 to March 2013
    Type
    Observational
    Phase
    Not applicable

    Participation criteria

    Sex
    Female
    Age
    Not applicable
    Accepts healthy volunteers
    none
    • Provided written informed consent for PGx research when they enrolled in the clinical study EGF105485 and did not withdraw consent prior to PGx experiment
    • Provided a blood sample for genotyping
    • Did not provide written informed consent for PGx research when they enrolled in the clinical study EGF105485, or withdrew their PGx consent prior to genotyping being conducted
    • Did not provide any or an adequate blood sample for genotyping
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Provided written informed consent for PGx research when they enrolled in the clinical study EGF105485 and did not withdraw consent prior to PGx experiment
    • Provided a blood sample for genotyping
    • Successfully genotyped for GWAS and candidate genes under study and pass quality control measures
    • Valid clinical data available
    Exclusion criteria:
    • Did not provide written informed consent for PGx research when they enrolled in the clinical study EGF105485, or withdrew their PGx consent prior to genotyping being conducted
    • Did not provide any or an adequate blood sample for genotyping
    • Failed genotyping
    • 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
    2013-08-03
    Actual study completion date
    2013-08-03

    Plain language summaries

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

    Additional information about the trial

    Not applicable
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