Metastatic Prostate CancerPARADIGMNCT04067713
Plasma Analysis for Response Assessment and to DIrect the manaGement of Metastatic Prostate Cancer
An observational study of Metastatic Prostate Cancer, run by University College, London at 16 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- How many people
- 192 participants
- Where
- 16 sitesUnited Kingdom
- Study dates
- 20 Sep 2019to 31 Oct 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Able and willing to provide written informed consent
- Aged 18 or over
- Polymetastatic disease defined as one of the following:
- ≥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).
Show all 11Show fewer
- Patients should be either of the following:
- 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.
Who cannot join
- 1 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).
- 2. Prior systemic therapy for prostate cancer other than for LHRHa +/- anti-androgen (started within the time limits defined in inclusion criterion 7).
- 3. Metastatic brain disease or leptomeningeal disease.
- 4. Any surgery planned prior to Cycle 4 Day 1 (C4 D1)
- 5. 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).
- 6. Patients who consent to the whole-body magnetic resonance imaging (WBMRI) translational sub-study should have no contraindications to MRI as per local guidelines.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United Kingdom16 sites
Aberdeen Royal Infirmary
Aberdeen, AB15 6RE
Royal Bournemouth Hospital
Bournemouth, BH7 7DW
Velindre University NHS Trust
Cardiff, CF15 7QZ
Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust
Doncaster, DN2 5LT
Medway NHS Foundation Trust
Gillingham, ME7 5NY
The Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, CH63 4JY
The Princess Alexandra Hospital NHS Trust
London, CM20 1QX
Barts Health NHS Trust, Royal London Hospital
London, E1 1FR
Kingston Hospital NHS Foundation Trust
London, KT2 7QB
Royal Free London NHS Foundation Trust
London, NW3 2QG
Guy's and St Thomas's NHS Foundation Trust
London, SE1 9RT
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
University College London Hospital
London, W1T 4TJ
The Christie NHS Foundation Trust
Manchester, M20 4BX
University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD
About this study
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.
Read more
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.
Read the detailed description
In the UK, prostate cancer is the most common cancer in men and with about 1 in 8 men diagnosed with prostate cancer in their lifetime. Up to a third of prostate cancer deaths occur when cancer spreads to other parts of the body known as metastatic prostate cancer, which is a major healthcare burden. Currently, physicians use a maximum of six cycles of Docetaxel and continue Androgen Receptor Signalling Inhibitor (ARSI) drugs until disease progression with long term androgen deprivation therapy (ADT).
There is no early test to indicate if treatment is working for patients with metastatic prostate cancer. Currently Prostate Specific Antigen (PSA) is not sensitive enough to guide treatment alone. Studies in colorectal, lung and prostate cancers have started looking at substance called Plasma tumour deoxyribonucleic acid (ptDNA) and correlated presence of ptDNA will early relapse. Therefore, this study will investigate if the detection of ptDNA after initiating treatment is associated a worse clinical outcome. Our ultimate aim, is to identify which of the current treatment options will work best for patients in the future. This research may also identify new targets for the development of new drugs to test in clinical trials in the future.
Assessments will include blood taken before and during treatment and at cancer progression. In selected centres, an optional Whole Body Magnetic Resonance Imaging (WBMRI) will be performed before and during treatment for those patients who are eligible. Patients will be followed up for a maximum of 10 years at the time they register onto the study. We expect recruitment duration to be 18 months.
- Conditions
- Metastatic Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Symptomatic or asymptomatic new or unequivocal progression of prior distant metastases confirmed by imaging
- Symptomatic progression of cancer in the prostate confirmed by imaging
- Serum PSA progression in PARADIGM-D
- Death from any cause
OS is defined as time from start of ARSI or docetaxel with ADT to death from any cause.
Measured: 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)
Prostate Cancer Specific Survival (PCSS) defined as time from start of ARSI or docetaxel with ADT to death from prostate cancer
Measured: 10 years after last patient has been registered
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start20 Sep 2019
- Primary completion31 Oct 2030 (estimated)
- Study completion31 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Epic Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04067713
- Sponsor's protocol ID
- UCL/18/0513
- Acronym
- PARADIGM
- Status last verified
- May 2026
- First submitted
- 24 Jul 2019
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Jayaram A, Rashid M, Reid AHM, Orlando F, Thakali S, Zakka L, Goncalves M, O'Dwyer J, Alifrangis C, Jones R, Pintus E, Needleman S, Bianchini D, Wingate A, Ng K, Linch M, McGovern U, Staffurth J, Crabb SJ, Brock S, Birtle A, Vainauskas O, Leone G, Chiwewe M, Hackshaw A, Lopes A, Wetterskog D, Demichelis F, Attard G. Combined ctDNA and serum PSA for dynamic monitoring of metastatic prostate cancer starting first-line treatment: a prospective national cohort study. Nat Cancer. 2026 Jun;7(6):915-927. doi: 10.1038/s43018-026-01172-9. Epub 2026 May 15.
PubMed 42141175
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Analysis for Response Assessment and to DIrect the manaGement of Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT04067713
- Acronym / sponsor ID
- PARADIGM / UCL/18/0513
- Conditions
- Metastatic Prostate Cancer
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 192 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Epic Sciences
- Study start
- 20 Sep 2019 (actual)
- Primary completion
- 31 Oct 2030 (estimated)
- Study completion
- 31 Oct 2030 (estimated)
- First posted
- 26 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In the UK, prostate cancer is the most common cancer in men and with about 1 in 8 men diagnosed with prostate cancer in their lifetime. Up to a third of prostate cancer deaths occur when cancer spreads to other parts of the body known as metastatic prostate cancer, which is a major healthcare burden. Currently, physicians use a maximum of six cycles of Docetaxel and continue Androgen Receptor Signalling Inhibitor (ARSI) drugs until disease progression with long term androgen deprivation therapy (ADT).
There is no early test to indicate if treatment is working for patients with metastatic prostate cancer. Currently Prostate Specific Antigen (PSA) is not sensitive enough to guide treatment alone. Studies in colorectal, lung and prostate cancers have started looking at substance called Plasma tumour deoxyribonucleic acid (ptDNA) and correlated presence of ptDNA will early relapse. Therefore, this study will investigate if the detection of ptDNA after initiating treatment is associated a worse clinical outcome. Our ultimate aim, is to identify which of the current treatment options will work best for patients in the future. This research may also identify new targets for the development of new drugs to test in clinical trials in the future.
Assessments will include blood taken before and during treatment and at cancer progression. In selected centres, an optional Whole Body Magnetic Resonance Imaging (WBMRI) will be performed before and during treatment for those patients who are eligible. Patients will be followed up for a maximum of 10 years at the time they register onto the study. We expect recruitment duration to be 18 months.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (11 listed)
- Able and willing to provide written informed consent
- Aged 18 or over
- Polymetastatic disease defined as one of the following:
- 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).
Key exclusion criteria (7 listed)
- 1 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).
- 2. Prior systemic therapy for prostate cancer other than for LHRHa +/- anti-androgen (started within the time limits defined in inclusion criterion 7).
- 3. Metastatic brain disease or leptomeningeal disease.
- 4. Any surgery planned prior to Cycle 4 Day 1 (C4 D1)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Progression Free Survival (PFS) and Overall Survival (OS) for PARADIGM-A, PARADIGM-D and PARADIGM-E.
Time frame: 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
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.
1 secondary outcome
Prostate Cancer Specific Survival (PCSS)
Time frame: 10 years after last patient has been registered
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Derived from this study: PubMed 42141175Jayaram A, Rashid M, Reid AHM, Orlando F, Thakali S, Zakka L, Goncalves M, O'Dwyer J, Alifrangis C, Jones R, Pintus E, Needleman S, Bianchini D, Wingate A, Ng K, Linch M, McGovern U, Staffurth J, Crabb SJ, Brock S, Birtle A, Vainauskas O, Leone G, Chiwewe M, Hackshaw A, Lopes A, Wetterskog D, Demichelis F, Attard G. Combined ctDNA and serum PSA for dynamic monitoring of metastatic prostate cancer starting first-line treatment: a prospective national cohort study. Nat Cancer. 2026 Jun;7(6):915-927. doi: 10.1038/s43018-026-01172-9. Epub 2026 May 15.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Prostate Cancer, run by University College, London at 16 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) and Overall Survival (OS) for PARADIGM-A, PARADIGM-D and PARADIGM-E. (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04067713, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.