Prostate Cancer Genomic Heterogeneity

NCT02022371 | Completed Phase 1

• 1 other identifier: 13/0244
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to carry out very detailed genetic testing on prostate cancer cells. The reason to do this is because researchers do not fully understand

• How prostate cancer develops
• Why some cancer cells spread and others do not
• Why some cancer cells respond to treatment and others do not Researchers and doctors know that 1 in 3 of the male population over the age of 50 has cancer cells in their prostate. However, most of these men will never know they have it and it will not affect their quality of life or their life expectancy. However, some cancers can be aggressive. These are more likely to spread outside of the prostate and cause problems. Doctors do not have an accurate way to tell the difference between aggressive cancer and those which will not cause any problems. Even within one prostate some tumours are aggressive and others do not cause a problem during the lifetime of a patient. In fact, even within one tumour, different cells may behave differently. In other words, one part of the tumour may be aggressive and spread, whilst another part of the same tumour does not. This project will try to find out more about what makes different tumours and different parts of the same tumour aggressive or harmless. It is important to find out what makes some cancer cells spread and others stay where they are. For the investigators to do this they need to collect fresh samples of cancer tissue from the prostate and from different areas of a tumour within the prostate. This is because biopsies used to diagnose or exclude cancer by the hospital laboratory are not good enough to give investigators detailed genetic information. These biopsies have been put into a chemical called formalin which reduces the quality of the genetic information. Investigators are therefore asking patients who are undergoing prostate biopsies as part of their normal care to allow them to take additional biopsies for the purpose of this study. This may be the first time patients are having biopsies. Or, patients may be having biopsies after treatment that has been given for the cancer and the doctors are concerned the treatment is not working.

Conditions

PROSTATE CANCER

Outcome Measures

Primary Outcomes (3)

• Tumour heterogeneity

  To define the extent of inter/intra-tumour heterogeneity and its association with disease stage at diagnosis and Gleason grade by deep genomic sequencing of multiple regions of intermediate Gleason grade tumours and high Gleason grade tumours, with and without metastatic disease.

  At time of biopsy

• Clonal origin of secondary tumours

  Through clonal re-ordering and multi-regional prostate mapping, determine whether satellite tumour nodules in high grade prostate cancers represent monoclonal disease related to the index lesion or the evolution of polyclonal cancers by evaluating the deep genomic signatures of primary and secondary lesions within the prostate

  At time of biopsy

• Relationship of tumours to metastases

  Identify genotype requirements for metastasis development by deep sequencing DNA from the associated metastases from the same patient to reconstruct clonal evolution from primary tumour to metastatic sites and identify evolutionary bottlenecks governing metastasis development that may be targetable for clinical benefit.

  At time of biopsy

Secondary Outcomes (3)

• Identifying genomic signature of tumour DNA in blood

  At time of biopsy

• Genomic signature changes in tumour DNA in blood when drug resistance develops

  At time of biopsy

• Relationship of tumour genomics with imaging

  At time of biopsy

Study Arms (1)

Targeted biopsy

EXPERIMENTAL

Snap frozen targeted biopsies of the prostate for genomic analysis

Procedure: Targeted biopsies of the prostate

Interventions

Targeted biopsies of the prostate PROCEDURE

Multiple biopsies from a MRI lesion for analysis of intratumour heterogeneity

Also known as: SmartTarget Biopsies of the prostate for snap frozen tissue in order to obtain genetic heterogeneity

Targeted biopsy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment naïve group
• Men with no prior diagnosis of prostate cancer undergoing prostate biopsy based on identified lesions on imaging
• Men with a raised PSA above 15ng/ml
• Men giving informed consent
• Treated men
• Men undergoing tissue biopsy for suspicion of prostate cancer recurrence following previous local or systemic therapy based on identified lesions in multi-parametric MRI, bone-scan, choline PET/CT, or PET/MRI

You may not qualify if:

• \. Unable to have MRI scan or CT scan, or in whom artefact would reduce scan quality
• Unable to have prostate biopsy
• Unable to undergo biopsy for metastatic evaluation
• On immunosuppression or predefined immunosuppressed state
• A coagulopathy predisposing to bleeding
• Unable to give informed consent

Sponsors & Collaborators

• University College London Hospitals: lead

Study Sites (1)

University College London Hospitals

London, NW1 2BU, United Kingdom

Location

Related Publications (1)

• Linch M, Goh G, Hiley C, Shanmugabavan Y, McGranahan N, Rowan A, Wong YNS, King H, Furness A, Freeman A, Linares J, Akarca A, Herrero J, Rosenthal R, Harder N, Schmidt G, Wilson GA, Birkbak NJ, Mitter R, Dentro S, Cathcart P, Arya M, Johnston E, Scott R, Hung M, Emberton M, Attard G, Szallasi Z, Punwani S, Quezada SA, Marafioti T, Gerlinger M, Ahmed HU, Swanton C. Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters. Ann Oncol. 2017 Oct 1;28(10):2472-2480. doi: 10.1093/annonc/mdx355.

  PMID: 28961847 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MRC Clinician Scientist

Study Record Dates

• First Submitted: December 15, 2013
• First Posted: December 27, 2013
• Study Start: September 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: May 10, 2017

Record last verified: 2017-05

Locations

GB (1)