Plasma Analysis for Response Assessment and to DIrect the manaGement of Metastatic Prostate Cancer

NCT04067713 | Active Not Recruiting DMC

• 1 other identifier: UCL/18/0513
• Study Type: observational
• Target: 192
• Locations: 1 country
• Sites: 16

Brief Summary

This research study is looking into plasma tumour deoxyribonucleic acid (ptDNA), a substance that is shed by cancer cells and can be detected in blood samples. Analysing ptDNA may therefore be able to provide more information about the characteristics of prostate cancer. This study will involve taking additional blood samples during standard treatment. The samples will be analysed in laboratories for levels of Prostate Specific Antigen (PSA); which gives information on the activity of the cancer; ptDNA; circulating tumour cells (ones that are derived from the cancer) (CTCs) and cells that affect immune system. The PARADIGM study is not, therefore, testing a new drug. Instead, the study is investigating if a new blood test can provide information about which current treatments for prostate cancer will work best for future patients with this disease. In the future and PARADIGM's ultimate aim is to identify which of the current treatment options will work best for patients. The research may also identify new opportunities for the development of drugs potentially useful in treating prostate cancer.

Conditions

Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) and Overall Survival (OS) for PARADIGM-A, PARADIGM-D and PARADIGM-E.

  PFS is defined as the interval from start of ARSI or docetaxel to disease failure as determined by at least one or more of these factors: 1. Symptomatic or asymptomatic new or unequivocal progression of prior distant metastases confirmed by imaging 2. Symptomatic progression of cancer in the prostate confirmed by imaging 3. Serum PSA progression in PARADIGM-D 4. Death from any cause OS is defined as time from start of ARSI or docetaxel with ADT to death from any cause.

  Following completion of cycle 3 or 4 of each patient - PARADIGM A & E, cycle length is 28 days. PARADIGM D, cycle length is 21 days. For OS, 10 years after last patient has been registered

Secondary Outcomes (1)

• Prostate Cancer Specific Survival (PCSS)

  10 years after last patient has been registered

Study Arms (3)

PARADIGM-D

Newly diagnosed metastatic prostate cancer patients starting long term therapy with Docetaxel with androgen deprivation therapy (ADT).

PARADIGM-A

Newly diagnosed metastatic prostate cancer patients starting long term therapy with Androgen Receptor Signalling Inhibitor (ARSI) drugs with androgen deprivation therapy (ADT).

PARADIGM-E

Newly diagnosed metastatic prostate cancer patients starting long term therapy with Enzalutamide with androgen deprivation therapy (ADT).

Eligibility Criteria

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

Study Population

Newly diagnosed metastatic prostate cancer patients starting long term therapy with either Androgen Receptor Signalling Inhibitor (ARSI) drugs (PARADIGM A) or Docetaxel (PARADIGM D) with androgen deprivation therapy (ADT). This is a UK based trial recruiting from approximately 20 sites over 36 months with a maximum follow up for 10 years. Patients will be screened at Multi disciplinary teams, and patient clinic appointments and those who fulfill eligibility criteria will be offered to take part. They will be given the patient information sheet (PIS) to take away and read and discuss with family and friends. They will be given the opportunity to ask questions before they consent. If the patient wishes, consent can happen on the same day as the PIS was given.

You may qualify if:

• Able and willing to provide written informed consent
• Aged 18 or over
• Polymetastatic disease defined as one of the following:
• i. ≥5 bone metastases ii. ≥1 unequivocal visceral metastases
• Eastern Cooperative Oncology Group (ECOG) Performance status 0 to 2
• No medical contra-indications to an Androgen receptor signalling inhibitor (ARSI) or docetaxel (with or without prednisolone).
• Patients should be either of the following:
• i. Planned to start long-term Luteinizing hormone Releasing Hormone (LHRH) suppression, or ii. Have started long-term LHRH antagonist within the last 14 weeks, or iii. Have started LHRH agonist within the last 16 weeks. When antiandrogens (eg bicalutamide) are used in combination with an LHRH agonist to prevent flare, patients have to have started within 18 weeks of starting antiandrogens..
• Patients should be planned for addition of docetaxel (PARADIGM-D) or ARSI (PARADIGM-A) within 14 weeks after start of LHRH antagonist ( 16 weeks if LHRH agonist is started without anti-androgen) or 18 weeks from start of anti-androgen with a target of 6 cycles or continuation until progression respectively.
• No concomitant medical conditions likely to reduce life expectancy.
• Patient agrees to be followed up in the recruiting centre and to having sequential plasma samples collected as per the study protocol.

You may not qualify if:

• Concurrent or planned for (i.e. prior to development of castration resistance), treatment with oestrogen, radiotherapy or surgery to the primary tumour.
• (N.B Patients may also be eligible if randomised to any of the following experimental drugs; PARPi, PD-1/PD-L1 , AKTi, PSMA-lutetium, if given in combination with SOC(i.e. ADT + docetaxel or ARSI) treatment in an open-label clinical trial, or to the placebo arm in an open-label clinical trial following discussion and approval of the CI/delegate. Patients can participate in other observational studies).
• \. Metastatic brain disease or leptomeningeal disease.
• \. Any surgery planned prior to Cycle 4 Day 1 (C4 D1)
• \. Other current malignancy or malignancy diagnosed or relapsed within the past 5 years (other than non-melanomatous skin cancer, stage 0 melanoma in situ and non-muscle invasive bladder cancer).
• \. Patients who consent to the whole-body magnetic resonance imaging (WBMRI) translational sub-study should have no contraindications to MRI as per local guidelines.

Sponsors & Collaborators

• University College, London: lead
• Epic Sciences: collaborator

Study Sites (16)

Aberdeen Royal Infirmary

Aberdeen, AB15 6RE, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Velindre University NHS Trust

Cardiff, CF15 7QZ, United Kingdom

Location

Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust

Doncaster, DN2 5LT, United Kingdom

Location

Medway NHS Foundation Trust

Gillingham, ME7 5NY, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, CH63 4JY, United Kingdom

Location

The Princess Alexandra Hospital NHS Trust

London, CM20 1QX, United Kingdom

Location

Barts Health NHS Trust, Royal London Hospital

London, E1 1FR, United Kingdom

Location

Kingston Hospital NHS Foundation Trust

London, KT2 7QB, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Guy's and St Thomas's NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

University College London Hospital

London, W1T 4TJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

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: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: August 26, 2019
• Study Start: September 20, 2019
• Primary Completion: November 30, 2024
• Study Completion (Estimated): October 1, 2030
• Last Updated: December 6, 2024

Record last verified: 2024-01

Locations

GB (16)