Information on Sub Studies

Germline DNA Analysis (Saliva Samples)

In collaboration with Professor Ros Eeles, Institute of Cancer Research, London, DNA is being extracted from saliva samples provided by consenting patients enrolled in STAMPEDE. The aims of this sub-study are to examine the germline (inherited) genetic changes present in men with high-risk localised or metastatic prostate cancer. The aim is to determine the prevalence of germline genetic aberrations present pre-diagnosis and to correlate prostate cancer risk Single nucleotide polymorphism (SNP) genetic profiles, identified in Genome-wide Association Studies (GWAS) and other sequence variants from next generation sequencing (NGS), with duration of response to ADT and the experimental treatments tested in STAMPEDE.

Circulating Tumour-DNA Analysis (Sequential Blood Samples)

This sub-study is being conducted in collaboration with Dr Gerhardt Attard, Institute of Cancer Research, London. The aims of this analysis include; identifying molecular subgroups with differential treatment effects and, identifying molecular changes associated with disease progression to explore resistance mechanisms and early detection of treatment failure.

From protocol version 19 (activated from Nov-2018 onwards), sequential blood samples were collected from patients within the “enzalutamide + abiraterone” comparison, i.e. allocated to arm A or J between 29-Jul-2014 and 31-Mar-2016. Genetic material shed by the tumour cells will be extracted, enabling tumour DNA analysis from the sequential blood samples.

Tissue Sample Analysis (FFPE Blocks)

As the clinical outcome data matures for several of the treatments comparisons evaluated within STAMPEDE, correlative analysis of the archival formalin-fixed paraffin-embedded (FFPE) tumour tissue will be undertaken, aiming to identify predictive and prognostic biomarkers. Targeted next generation sequencing (tNGS) of FFPE tumour samples from selected, consenting STAMPEDE patients will be performed in order to explore the prevalence of genomic aberrations and examine the predictive and prognostic effect of molecular sub-groups.

All patients joining the trial were asked to consent for the use of remaining tissue samples e.g. those obtained at prostate biopsy or following surgery, for use in additional research. These samples are usually stored as FFPE tissue blocks at the hospital where the procedure was performed. Sites were asked to assist in the retrieval of tissue samples stored in pathology stores or referring hospitals when these are required for additional translational sub-studies. All patients who consented to part C on the additional research consent form were eligible for on-going sub-studies involving FFPE tumour block analysis. For patients who previously joined the trial, consent for use of remaining samples was provided in part L of the informed consent form. Prior to FFPE sample transfer, a material transfer agreement was required to be in place between the sponsor and the site. Further details on the sample processing and transfer can be found in the Sample Collection and Handling Manual (found on the Training Materials & Resources page).

Biomarker-Screening Pilot

A selection of STAMPEDE centres were invited to participate in the Biomarker-Screening Pilot. The aim of this Pilot was to test the processes involved in pre-randomisation Biomarker Screening.

Tissue, saliva and blood samples were collected from 100 participants and tested for a panel of possible gene mutations. Sample collection and testing has been completed, and patients with clinically significant genetic mutations have been contacted where appropriate by their research teams in order to refer them to a genetic counsellor.

We would like to thank all of the teams, participants and their families that took part in the Biomarker-Screening Pilot. For further information regarding the Pilot and it’s outcomes please review the publication.