Biomarker development in prostate cancer: a sub-study of STAMPEDE

  • Research type

    Research Study

  • Full title

    Developing prognostic and predictive biomarkers in prostate cancer using archival tissue from STAMPEDE participants: a sub-study of STAMPEDE

  • IRAS ID

    203620

  • Contact name

    Clare Gilson

  • Contact email

    c.gilson@ucl.ac.uk

  • Sponsor organisation

    MRC Clinical Trials Unit at UCL

  • Duration of Study in the UK

    1 years, 5 months, 29 days

  • Research summary

    Prostate cancer is a highly heterogeneous disease with a growing number of treatment options. Yet despite increased understanding of tumour biology, prostate cancer management lags behind that of other cancers due to the lack of predictive biomarkers.

    Integration of clinical and translational research is urgently needed to develop biomarkers able to inform treatment selection and provide a rationale for additional targeted strategies.

    Systematic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) is an ongoing multi-centre randomised controlled trial for men with locally-advanced or metastatic prostate cancer. Using a multi-arm, multi-stage (MAMS) platform design STAMPEDE will evaluate at least 9 treatment strategies. Analysis of the archival tumour tissue from randomised comparisons within STAMPEDE offers a unique opportunity to support biomarker development through associated translational sub-studies.

    In collaboration with Almac diagnostics and Clovis Oncology this sub-study will undertake three analyses aiming to assess the clinical utility of three biomarkers of interest.
    Analysis one aims to validate a prognostic biomarker in men presenting with localised prostate cancer. By comparing relapse rates in biomarker positive patients within a randomised comparison of docetaxel vs. hormone treatment alone, we will aim to determine if this biomarker can be used to predict who will benefit from adjuvant docetaxel.

    Genetic defects in DNA repair mechanisms have been shown to be present in around 20% of advanced prostate cancers; the prevalence in newly diagnosed disease remains unknown. We will evaluate two biomarkers that have been developed in other tumour types. Analyses two will evaluate genomic LOH, a biomarker developed in ovarian cancer. Analysis three will evaluate DNA damage response deficiency (DDRD) which was developed in breast cancer.

    We will aim to determine the feasibility of using these assays in archived prostate core biopsies and determine how common this genetic problem is in newly diagnosed metastatic disease. We will then characterise this group of prostate cancers and aim to determine if they respond differently to docetaxel, the new standard-of-care. If shown to benefit less, this will provide a rationale for evaluating alternative treatment strategies in this group.

  • REC name

    West Midlands - Edgbaston Research Ethics Committee

  • REC reference

    16/WM/0188

  • Date of REC Opinion

    22 Apr 2016

  • REC opinion

    Favourable Opinion