Exploring the Mechanisms and Dynamics of Clonal Evolution Leading to Recurrence in Prostate Cancer

NCT ID: NCT04686188

Last Updated: 2020-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-26

Study Completion Date

2022-09-01

Brief Summary

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Prostate cancer is the most common cancer in males in the UK, and current estimates are that 1 in 8 will be diagnosed with prostate cancer in their lifetime. Although surgery or radiotherapy with hormone therapy offers a good chance of cure in localised disease, recurrence can occur, which may cause significant distress, and may shorten the patient's life. In patients with locally advanced disease (disease that has broken through the surrounding capsule of the prostate gland), around 30-40% of patients experience a recurrence.

Cancer develops as a result of normal cells acquiring genetic mutations, and localised prostate cancer at diagnosis is commonly made up of different subclones - distinct regions within the patient's cancer with different sets of genetic mutations, each of which may behave differently and be more or less sensitive to treatments.

The IMRT clinical trial (CCR 1766) recruited 486 patients who received hormone therapy and radiotherapy to the prostate and lymph nodes in patients with locally advanced prostate cancer. The FORECAST study (FORecasting the Evolution of CAncer of the proState within a Trial) is undertaking genetic sequencing of several regions of these patients' prostate cancers in order to determine which subclones are present at diagnosis, and how they evolved. FORECAST also has permission to obtain and perform sequencing on primary samples from two other large trials in localized prostate cancer.

This study seeks to collect blood samples from patients who have experienced a recurrence in whom the primary biopsies have been sequenced as part of FORECAST. Additionally, blood will be collected from any patient in follow up at The Royal Marsden who received radiotherapy and hormone therapy for a localised prostate cancer and has experienced a recurrence but not yet started treatment. In these patients, the FORECAST protocol will be used to undertake genetic sequencing of their original prostate cancer biopsies. Genetic mutations from the cancer can be detected in the blood in patients who relapse, so-called 'liquid biopsies'. By comparing the genetic information between the primary and relapsed cancer, we can detect which subclones present at diagnosis are ultimately responsible for the cancer relapsing, and help us to understand the evolution of prostate cancers over time. This will assist us in predicting at the point of diagnosis which patients are more likely to relapse, so that we may consider escalating primary treatments or treating patients with high-risk subclonal mutations with targeted therapies upfront. As a result, we aim to reduce the number of patients treated for localised prostate cancer experiencing a recurrence. Additionally, although liquid biopsies are well-characterized in metastatic prostate cancer, little is known about their value in patients who have a biochemical-only relapse (patients who have a rising PSA with no evidence of cancer on scans) and this will also be explored.

Detailed Description

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Conditions

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Prostate Cancer Recurrent

Keywords

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Prostate cancer Liquid biopsy Circulating tumor DNA Intratumor Heterogeneity Prostate radiotherapy Recurrent prostate cancer

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

1. Male aged ≥18 years
2. Prostate tumour biopsy specimens available at The Royal Marsden Hospital, Kingston Hospital, Epsom and St Helier Hospitals, St George's Hospital or Croydon University Hospital and \>2 primary tumour regions sampled
3. Received primary radical radiotherapy and androgen deprivation therapy and remains under follow up at The Royal Marsden Hospital
4. Willing and able to comply with blood sample collection
5. Capable of understanding and complying with the protocol requirements and has given written, dated and signed informed consent AND
6. Confirmed biochemical or radiological evidence of recurrent prostate cancer, and not yet received treatment for recurrent disease OR
7. FORECAST patients with confirmed biochemical or radiological evidence of recurrent prostate cancer who have received or are currently receiving treatment but are progressing (rising PSA and/or evidence of progressive disease on imaging), or have a PSA \>2ng/ml

Exclusion Criteria

1\. Patients who have had another malignancy (excluding non-melanoma skin cancer, in-situ or superficial bladder cancer) treated within the previous 5 years
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrea Sottoriva, BSc MSc PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Cancer Research, United Kingdom

Locations

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Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Katharine C Webb, BSc MBBS MSc

Role: CONTACT

Phone: +4420 8722 4504

Email: [email protected]

Andrea Sottoriva, BSc MSc PhD

Role: CONTACT

Phone: +442087224072

Email: [email protected]

Facility Contacts

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Katharine C Webb, BSc MBBS MSc

Role: primary

Julia Murray, PhD FRCR

Role: backup

Other Identifiers

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275583

Identifier Type: OTHER

Identifier Source: secondary_id

CCR 5314

Identifier Type: -

Identifier Source: org_study_id