Information on Sub Studies

Each person’s genetic makeup influences the way they respond to any medical treatment, how well it works and what side effects occur.

One of the aims of the STAMPEDE trial is to collect DNA from prostate cancer patients for future research. With patient consent, saliva, blood and tissue samples from as any patients as possible will be collected for research.

These samples will be collected and stored for DNA and protein analysis in order to try to identify molecular features of clinical significance. We would like to see whether certain genes are associated either with certain side effects or with beneficial results from the study drugs. This research may help to predict which patients will benefit most from future treatments.

For details regarding sample collection, please refer to the Sample Collection and Handling Manual. (found on the Training Materials & Resources page).

Summary of when samples are collected for each STAMPEDE sub-study:

 

 

Translational Sub-Study

 

Sample Type

 

Patient Group

Pre-Progression(Weeks 48, 72 & 84)

 

Progression

 

 

Post-Progression, Pre-2nd Line Treatment

 

Saliva collection

(Germline DNA)

 

Saliva

 

All arms

   

X

can be taken any time after randomisation

  

Sequential blood collection

(Circulating tumour DNA)

 

Blood

 

Arms A and J

M1

 X

 X

 X

Blood

 

Arms A and J

M0

 N/A

 X

 X

Retrieval of FFPE block of archival tissue sample

FFPE block

All arms

X

may be requested any time after randomisation

 

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.

All patients enrolled in STAMPEDE since November 2011 are eligible for participation in this sub-study. All patients joining the trial are asked to consent to provide a saliva sample from which germline DNA can be extracted.

As the previous germline DNA extraction has been inadequate, we are now requesting that all patients who have joined the trial (all arms) since November 2011 are now invited to provide a saliva sample. Patients will need to re-consent for this using the additional consent form following review of the additional research PIS.

In addition as of 20 June 2017 activation of protocol version 16, patients can opt to consent to receive clinically significant genetic results. If patients would like to receive genetic results, they must be re-consented to the current of the additional research consent form (found on the Current Essential Documents page).

Saliva samples should be provided after randomisation and all consenting patients from all arms can participate.

 

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 are 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.

The sampling schedule is different for M0 and M1 patients and is detailed in the Sample collection and handling manual (found on the Training Materials & Resources page). Sequential samples are required in order to detect genetic changes within tumours over time. The most important sampling time point is at progression, as it is hoped this can inform the potential mechanisms of treatment resistance. From Protocol version 16 the sampling schedule had been updated to allow sample collection for each type of progression (biochemical, radiological and clinical).

The following table summarises the time points for sequential blood sample collection:

 

 

 

 

 

 

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. FFPE blocks are currently being collected at selected STAMPEDE sites to support different projects.

All patients joining the trial have been 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. Randomising sites will be 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 consent to part C on the additional research consent form are 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. Research teams at randomising sites will be required to provide an anonymised copy of the consent form required to request samples from pathology departments and facilitate the transfer of samples to the trial designated laboratories. Prior to FFPE sample transfer, a material transfer agreement is 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).

 

The following table describes the shipment addresses of each sample type. 

TRANSLATIONAL SUB-STUDY

SAMPLE TYPE

ADDRESS TO SHIP SAMPLE TO

 

Saliva collection

(Germline DNA)

 

Saliva

Professor Ros Eeles

STAMPEDE SALIVA

Institute of Cancer Research

15 Cotswold Place

Sutton

Surrey SM2 5NG

 

Sequential blood collection

(Circulating tumour DNA)

 Blood

STAMPEDE BLOOD

UCL Cancer Institute

UCL ECMC GCLP Facility

Paul O’Gorman Building

72 Huntley Street

London WC1E 6DD

 

Retrieval of FFPE block of archival tissue sample

 

FFPE block

Fiona Morgan

STAMPEDE BIOSAMPLES

Wales Cancer Bank

A2 Corridor, 2nd Floor, Main Building

University Hospital of Wales

Health Park

Cardiff CF14 4XN

 

Tissue Sample Analysis (FFPE Blocks)

A selection of STAMPEDE centres will be invited to participate in the Biomarker-Screening Pilot. This aims to test out the processes involved in pre-randomisation Biomarker Screening in preparation for the “rucaparib comparison. This new comparison will open later in the year and will test a PARP inhibitor, rucaparib, in men with metastatic prostate cancers with specific faults in DNA repair genes. Sites who successfully participate in the pilot will be accredited to open the “rucaparib comparison” first.

The following participants are eligible to join the Biomarker screening Pilot

  • Confirmed metastatic disease
  • FFPE block containing prostate cancer sample obtained within 8 months prior to registration
  • If hormone therapy has started, FFPE tumour blocks should be sent from sites for central review:
    • Within 8 weeks of the patient starting LHRH
    • Within 10 weeks of starting anti-androgens.
  • Written informed consent provided to participate in STAMPEDE and to participate in biomarker-screening, recorded on the Additional Research Consent Form
  • Registered at a STAMPEDE site participating in the Biomarker-Screening Pilot

Preliminary data from ongoing STAMPEDE translational sub-studies have demonstrated that it is feasible to sequence DNA and RNA extracted from standard formalin fixed paraffin embedded (FFPE) tumour blocks, saliva and blood samples from which circulating tumour DNA can be isolated. In the pilot phase we are assessing all three sample types, so at the point of registration the following should be sent:

  • Tumour rich FFPE blocks (ideally 2)
  • Saliva sample
  • Blood sample collected in cell free Streck™ tube

For further information please refer to Biomarker Screening Manual.

 

 

 

STAMPEDE

Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy

See the latest News in STAMPEDE through the link to the right.