Last updated: 11/03/2018 21:46:49

PGx7592: Evaluation of the Effect of BIM Germline Variants on Pazopanib Efficacy in Patients with Cancer

GSK study ID
201608
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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: PGx7592: Evaluation of the Effect of BIM Germline Variants on Pazopanib Efficacy in Patients with Cancer
Trial description: Pazopanib and sunitinib are anti-angiogenic, oral tyrosine kinase inhibitors (TKIs), both are approved for use in advanced or metastatic renal cell carcinoma (RCC). Pazopanib is also approved for use in advanced soft tissue sarcoma (STS), and sunitinib is approved for use in gastrointestinal stromal tumour and pancreatic neuroendocrine tumours. Currently, there is no validated biomarker that predicts response to treatment with either pazopanib or sunitinib.
A 2.9kb deletion polymorphism in the BIM gene was shown to be associated with resistance to gefitinib treatment in subjects with non-small cell lung cancer, and with resistance to imatinib treatment in subjects with chronic myeloid leukemia (Ng et al. Nat Med 2012; 18:521-8). This deletion has only been observed in individuals of East Asian descent. This pharmacogenetic (PGx) analysis will assess association between the BIM deletion and other putatively functional BIM polymorphisms and progression free survival (PFS), overall survival (OS) and best response in subjects received either pazopanib or sunitinib. The PGx analyses will using data from consented subjects in eight GSK clinical studies for advanced/metastatic RCC (VEG102616, VEG105192, VEG107769, VEG108844 and VEG113078), advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (VEG110655, VEG114012 ), and advanced STS (VEG110727). The primary analysis will test association between the BIM deletion and PFS in pazopanib-treated subjects of East or South-East (E/SE) Asian ancestry. Secondary analyses will test association between 1) the BIM deletion with OS and best response in pazopanib- treated subjects of E/SE Asian ancestry; 2) the BIM deletion and efficacy endpoints in sunitinib-treated subjects of E/SE Asian ancestry; 3) other putatively functional BIM polymorphisms with efficacy endpoints in pazopanib- or sunitinib-treated subjects of all ancestries. Cox proportional hazards model will be used to assess the association of genotype with PFS and OS. Ordinal regression will be conducted for best response. Summary statistics from genotyping/indications groups will be meta-analyzed using the inverse variance method.
Primary purpose:
Not applicable
Trial design:
Not applicable
Masking:
Not applicable
Allocation:
Not applicable
Primary outcomes:

Determine whether the BIM deletion is associated with PFS in East/South East Asian subjects with cancer

Timeframe: N/A

Secondary outcomes:

Determine association between BIM deletion with OS and best response in pazopanib- treated subjects, between BIM deletion and sunitinib efficacy, between other BIM polymorphisms and pazopanib or sunitinib efficacy.

Timeframe: N/A

Interventions:
  • Other: placebo
  • Drug: sunitinib
  • Drug: pazopanib
    • Enrollment:
    1
    Primary completion date:
    Not applicable
    Observational study model:
    Cohort
    Time perspective:
    Retrospective
    Clinical publications:
    Not applicable
    Medical condition
    Cancer, Neoplasms
    Product
    pazopanib
    Collaborators
    Not applicable
    Study date(s)
    August 2014 to October 2014
    Type
    Observational
    Phase
    Not applicable

    Participation criteria

    Sex
    Female & Male
    Age
    Not applicable
    Accepts healthy volunteers
    none
    • Subjects who provided written informed consent and a blood sample for PGx research in clinical studies VEG102616, VEG105192, VEG107769, VEG108844, VEG113078, VEG110655, VEG114012, VEG110727, were successfully genotyped for at least one genetic marker under study, and had clinical data available
    • Subjects who fail genotyping quality control
    • Subjects where gender inferred from his/her sex chromosome genotypes does not agree with the reported gender;
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subjects who provided written informed consent and a blood sample for PGx research in clinical studies VEG102616, VEG105192, VEG107769, VEG108844, VEG113078, VEG110655, VEG114012, VEG110727, were successfully genotyped for at least one genetic marker under study, and had clinical data available
    Exclusion criteria:
    • Subjects who fail genotyping quality control
    • Subjects where gender inferred from his/her sex chromosome genotypes does not agree with the reported gender;
    • Subjects where potential sample contamination is detected
    • Subjects who, based on genetic data, are determined to be duplicates, or first or second degree relatives, of other subjects included in the analysis

    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
    2014-17-10

    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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