Prostate CancerVALIDATE-PRONCT05017181
Novel MRI Assessment of Prostate Cancer VALIDATE-PRO
An observational study of Prostate Cancer, run by University College, London at 1 site in United Kingdom.
Trial summary
For 50 years the diagnosis of prostate cancer has been with Prostate Specific Antigen (PSA) blood testing and prostate biopsy. However, this approach resulted in over-diagnosis, over-treatment and missed clinical important cancers. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- How many people
- 234 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Jan 2021to 1 Jun 2024
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
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: BioVal Cohort: Men scheduled for Prostatectomy ProVal Cohort: Men initiating active surveillance and treatment for low grade disease.
Who may be able to join
- Men aged >18 years
- Pre-biopsy mp-MRI study performed within preceding 4 months
- Likert/PIRADS score 4-5/5 lesion and/or biopsy confirmed Prostate cancer
- Willing and able to provide written informed consent
Who cannot join
- Men who suffer with claustrophobia or are unable to have an MRI e.g. implantable defibrillator, brain aneurysm clips or other implant, severe obesity or unable to lay still for length of scan.
- Men with an impaired renal function (eGFR <30)
- Previous prostate radiotherapy/focal treatment
- Hormonal treatment for prostate cancer within preceding 3 months from consenting to the study.
- Dementia or other neurological condition meaning participant lacks the capacity to consent.
Trial locations and contacts
1 site in 1 country.
Trial Manager contact
United Kingdom1 site, 1 recruiting
- Recruiting
University College London
London
Adam Retter, MD, 7398762767 ext. +044, rmharet@ucl.ac.uk
About this study
Official title: Assessment of Diagnostic and Prognostic VALue, Identification of bIological Correlates, and Determination of TEchnical Performance of Novel Metabolic and Microstructural MRI in PROstate Cancer
For 50 years the diagnosis of prostate cancer has been with Prostate Specific Antigen (PSA) blood testing and prostate biopsy. However, this approach resulted in over-diagnosis, over-treatment and missed clinical important cancers. Multi-parametric MRI (mp-MRI) has provided a solution to some of these issues and the National Institute for health and Care Excellence has advocated the use of mp-MRI before biopsy in men with a suspicion for prostate cancer.
However, important challenges remain and the current way we pick up and assess prostate cancer can be improved. mp-MRI can miss significant cancer in around 11% of cases, 30% of positive MRI scans turn out not to have significant cancer at biopsy. Lastly, 34% of mp-MRI lesions are scored as in-determinant which sometimes makes decisions for further investigation and treatment unclear.
Read more
There are also difficulties predicting patients who will have progression of their disease or those who will not suffer harm from their cancer. Therefore the development of non-invasive tests and markers that can tell apart aggressive and non-aggressive disease would be extremely useful in deciding what treatment approach suits individual patients.
This study will investigate the use of three different novel MRI methods; Vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT), Luminal Imaging (LI) and hyperpolarised [1-13C]-pyruvate MRI (HYP-MRI). These scans help us to look at the microstructure as well as the metabolism of prostate tissue and may offer ways to better differentiate aggressive vs non-aggressive disease.
These scans will be performed in men with prostate cancer suitable for active surveillance at baseline and 1 year later to assess for prognostic indicators for progression in early prostate cancer.HYP-MRI will also be performed in men undergoing radical prostatectomy for validation of image findings and pathology. Whilst some men will have repeat scanning to asses for the repeatability of these techniques.
Read the detailed description
PURPOSE AND DESIGN
The purpose of this study is to assess the ability of novel MRI techniques and their derived metrics in the diagnosis and prognostication of prostate cancer. Improving the diagnostic accuracy and investigating biomarkers with non- invasive MRI techniques have the promise of reducing unnecessary biopsies or radical treatment, as well as detecting those likely to progress at an earlier stage.
Vascular, Extracellular and Restricted Cytometry in Tumours (VERDICT) MRI
Diffusion-weighted imaging (DWI) is one of the most important sequences in mp-MRI of the prostate which reflects the diffusivity of water in cells and differs in cancerous tumour due to changes in cellular density, size, shape and arrangement. VERDICT is a novel framework which uses a more complex 3-compartment tissue model for diffusion of water; 1. Water trapped in cells, 2. Water in the vascular network and 3. Interstitial water. This allows us to make estimates of specific tissue properties such as the size and packing density of the cells, the vascular extracellular- extravascular space (EES) volume fractions. This methods is more biologically specific compared to conventional DWI. Studies in tumour xenograft models of colorectal cancer showed its ability to detect such known differences in the microstructure. At UCL we have applied VERDICT to the prostates of 78 men and were able to successfully differentiate between benign or clinically insignificant cancer and clinically significant tumours. This technique can be applied on commercially available MRI scanners and requires no additional contrast agents or requirements for the patient compared to conventional mp-MRI of the prostate.
Luminal Index (LI) MRI
Using a multi-echo T2 sequence we can differentiate between the relatively long T2 values of the luminal space and the short T2 values of the stromal and epithelial cells to estimate the fractional volume of water in each MR voxel, the luminal water fraction (LWF). Studies have shown a good correlation between LWF and histologically measure luminal fractional volume and hence promise to detect prostate cancer and predict Gleason score. Our refined local LI MRI sequence has been very good at differentiating clinically significant and non-significant tumours. This technique also requires no additional contrast agents or patient requirements to be completed.
Hyperpolarised [1-13C]-pyruvate MRI (HYP-MRI)
Cancer cell rely on enhanced glycolysis for their energy supply, a phenomenon known as the Warburg effect. This is a key discriminator of malignancy and normal tissues and has been successfully targeted with well-established imaging techniques such as Fluorodeoxyglucose (FDG) - Positron Emission Tomography (PET). HYP-MRI is able to image a part of this metabolic process in real-time. An injectable solution containing 13C labelled pyruvate which is hyperpolarised onsite in order to increase the eventual detectable signal. The naturally occurring metabolise pyruvate is converted to lactate with the attached 13C tag persisting enabling us to track the presence and conversion of pyruvate to lactate after the injection. It heralds the potential to differentiate tumours which are more likely to grow and metastasise from those which won't. This sequence requires an additional injection compared to standard mp-MRI and also uses an endorectal coil which is place inside the rectum for the duration of the scan.
The main objectives of this study are as follow and are addressed in three sub-studies:
- To biologically validate HYP-MRI with correlation against biological measurements in men undergoing radical prostatectomy (BioVal: 44 patients)
- Clinical validation of novel MRI techniques (VERDICT/LI/HYP-MRI) derived measurements for differentiating patients with aggressive (progressive) and indolent (non-progressive) prostate cancer in men entering active surveillance (ProVal: 120 patients)
- Technical validation of novel MRI techniques (VERDICT/LI/HYP-MRI) through assessment of repeatability metrics from derived parameters (TecVal: 20 patients)
- Conditions
- Prostate Cancer
- Keywords
- MRI, biomarker, novel technique, cancer, validation
- Medical subject headings
- Prostatic Neoplasms, 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 |
|---|---|---|
| BioVal | BioVal is a single site validation study to determine the histological correlates underpinning signals derived from 13C-pyruvate HYP-MRI in men with known prostate cancer scheduled for prostatectomy. | |
| ProVal | ProVal is a single site, prospective, longitudinal observational cohort study to determine the prognostic value of signals derived from VERDICT, Luminal Index MRI and 13C-pyruvate HYP-MRI in men with known early prostate cancer on active surveillance. | |
| TecVal | TecVal is a multi-site validation study to determine the inter-site repeatability and intra-site reproducibility of signals derived from VERDICT, Luminal Index MRI and 13C-pyruvate HYP-MRI in men with known prostate cancer. |
What is being measured
The primary outcome is the main question the study is designed to answer.
ProVal Primary Objective
To determine the prognostic value of VERDICT metrics for risk classification of patients with early prostate cancer suitable for active surveillance.
Quantitive value: fIC (intracellular (IC) volume fraction) among others within model.
Measured: 3 years
ProVal Primary Objective
To determine the prognostic value of Luminal Index for risk classification of patients with early prostate cancer suitable for active surveillance.
Quantitive value: Luminal index
Measured: 3 years
ProVal Primary Objective
To determine the prognostic value of 13C-HYP-MRI for risk classification of patients with early prostate cancer suitable for active surveillance.
Quantitive value: Lactate and pyruvate ratio parameters.
Measured: 3 years
BioVal Primary Objective
To estimate the association of 13C-HYP-MRI derived quantitative metrics against histological features of prostate cancer.
Quantitive value: Lactate and pyruvate ratio parameters.
Measured: 3 years
BioVal Primary Objective
To estimate the association of 13C-HYP-MRI derived quantitative metrics against histological features of prostate cancer.
Quantitive value: Gleason Grade
Measured: 3 years
TecVal Primary Objective
Inter-site repeatability and intra-site reproducibility of signals derived from VERDICT, Luminal Index MRI and 13C-pyruvate HYP-MRI in men with known prostate cancer.
Metric: Repeatability and reproducibility co-efficients
Measured: 3 years
Secondary outcomes (1)
ProVal Secondary Objective
To examine the effects of histological progression of prostate cancer on VERDICT and LI-MRI quantitative metrics To determine whether baseline imaging metrics can predict time to radiological progression.
Metric: Gleason grade (used in combination with previous metrics discussed)
Measured: 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2021
- Study start29 Jan 2021
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 234 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shonit Punwani, MD PhD, Principal investigator, UCL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05017181
- Sponsor's protocol ID
- 129237
- Acronym
- VALIDATE-PRO
- Status last verified
- Jul 2022
- First submitted
- 17 May 2021
- Last updated
- 29 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Diagnostic and Prognostic VALue, Identification of bIological Correlates, and Determination of TEchnical Performance of Novel Metabolic and Microstructural MRI in PROstate Cancer
- ClinicalTrials.gov ID
- NCT05017181
- Acronym / sponsor ID
- VALIDATE-PRO / 129237
- Conditions
- Prostate Cancer
- Keywords
- MRI, biomarker, novel technique, cancer, validation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 234 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 29 Jan 2021 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Jun 2024 (estimated)
- First posted
- 23 Aug 2021 (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.
For 50 years the diagnosis of prostate cancer has been with Prostate Specific Antigen (PSA) blood testing and prostate biopsy. However, this approach resulted in over-diagnosis, over-treatment and missed clinical important cancers. Multi-parametric MRI (mp-MRI) has provided a solution to some of these issues and the National Institute for health and Care Excellence has advocated the use of mp-MRI before biopsy in men with a suspicion for prostate cancer.
However, important challenges remain and the current way we pick up and assess prostate cancer can be improved. mp-MRI can miss significant cancer in around 11% of cases, 30% of positive MRI scans turn out not to have significant cancer at biopsy. Lastly, 34% of mp-MRI lesions are scored as in-determinant which sometimes makes decisions for further investigation and treatment unclear.
There are also difficulties predicting patients who will have progression of their disease or those who will not suffer harm from their cancer. Therefore the development of non-invasive tests and markers that can tell apart aggressive and non-aggressive disease would be extremely useful in deciding what treatment approach suits individual patients.
This study will investigate the use of three different novel MRI methods; Vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT), Luminal Imaging (LI) and hyperpolarised [1-13C]-pyruvate MRI (HYP-MRI). These scans help us to look at the microstructure as well as the metabolism of prostate tissue and may offer ways to better differentiate aggressive vs non-aggressive disease.
These scans will be performed in men with prostate cancer suitable for active surveillance at baseline and 1 year later to assess for prognostic indicators for progression in early prostate cancer.HYP-MRI will also be performed in men undergoing radical prostatectomy for validation of image findings and pathology. Whilst some men will have repeat scanning to asses for the repeatability of these techniques.
Detailed description
PURPOSE AND DESIGN
The purpose of this study is to assess the ability of novel MRI techniques and their derived metrics in the diagnosis and prognostication of prostate cancer. Improving the diagnostic accuracy and investigating biomarkers with non- invasive MRI techniques have the promise of reducing unnecessary biopsies or radical treatment, as well as detecting those likely to progress at an earlier stage.
Vascular, Extracellular and Restricted Cytometry in Tumours (VERDICT) MRI
Diffusion-weighted imaging (DWI) is one of the most important sequences in mp-MRI of the prostate which reflects the diffusivity of water in cells and differs in cancerous tumour due to changes in cellular density, size, shape and arrangement. VERDICT is a novel framework which uses a more complex 3-compartment tissue model for diffusion of water; 1. Water trapped in cells, 2. Water in the vascular network and 3. Interstitial water. This allows us to make estimates of specific tissue properties such as the size and packing density of the cells, the vascular extracellular- extravascular space (EES) volume fractions. This methods is more biologically specific compared to conventional DWI. Studies in tumour xenograft models of colorectal cancer showed its ability to detect such known differences in the microstructure. At UCL we have applied VERDICT to the prostates of 78 men and were able to successfully differentiate between benign or clinically insignificant cancer and clinically significant tumours. This technique can be applied on commercially available MRI scanners and requires no additional contrast agents or requirements for the patient compared to conventional mp-MRI of the prostate.
Luminal Index (LI) MRI
Using a multi-echo T2 sequence we can differentiate between the relatively long T2 values of the luminal space and the short T2 values of the stromal and epithelial cells to estimate the fractional volume of water in each MR voxel, the luminal water fraction (LWF). Studies have shown a good correlation between LWF and histologically measure luminal fractional volume and hence promise to detect prostate cancer and predict Gleason score. Our refined local LI MRI sequence has been very good at differentiating clinically significant and non-significant tumours. This technique also requires no additional contrast agents or patient requirements to be completed.
Hyperpolarised [1-13C]-pyruvate MRI (HYP-MRI)
Cancer cell rely on enhanced glycolysis for their energy supply, a phenomenon known as the Warburg effect. This is a key discriminator of malignancy and normal tissues and has been successfully targeted with well-established imaging techniques such as Fluorodeoxyglucose (FDG) - Positron Emission Tomography (PET). HYP-MRI is able to image a part of this metabolic process in real-time. An injectable solution containing 13C labelled pyruvate which is hyperpolarised onsite in order to increase the eventual detectable signal. The naturally occurring metabolise pyruvate is converted to lactate with the attached 13C tag persisting enabling us to track the presence and conversion of pyruvate to lactate after the injection. It heralds the potential to differentiate tumours which are more likely to grow and metastasise from those which won't. This sequence requires an additional injection compared to standard mp-MRI and also uses an endorectal coil which is place inside the rectum for the duration of the scan.
The main objectives of this study are as follow and are addressed in three sub-studies:
- To biologically validate HYP-MRI with correlation against biological measurements in men undergoing radical prostatectomy (BioVal: 44 patients)
- Clinical validation of novel MRI techniques (VERDICT/LI/HYP-MRI) derived measurements for differentiating patients with aggressive (progressive) and indolent (non-progressive) prostate cancer in men entering active surveillance (ProVal: 120 patients)
- Technical validation of novel MRI techniques (VERDICT/LI/HYP-MRI) through assessment of repeatability metrics from derived parameters (TecVal: 20 patients)
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BioVal | – | –BioVal is a single site validation study to determine the histological correlates underpinning signals derived from 13C-pyruvate HYP-MRI in men with known prostate cancer scheduled for prostatectomy. |
| ProVal | – | –ProVal is a single site, prospective, longitudinal observational cohort study to determine the prognostic value of signals derived from VERDICT, Luminal Index MRI and 13C-pyruvate HYP-MRI in men with known early prostate cancer on active surveillance. |
| TecVal | – | –TecVal is a multi-site validation study to determine the inter-site repeatability and intra-site reproducibility of signals derived from VERDICT, Luminal Index MRI and 13C-pyruvate HYP-MRI in men with known prostate cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- BioVal Cohort: Men scheduled for Prostatectomy ProVal Cohort: Men initiating active surveillance and treatment for low grade disease.
Key inclusion criteria (4 listed)
- Men aged >18 years
- Pre-biopsy mp-MRI study performed within preceding 4 months
- Likert/PIRADS score 4-5/5 lesion and/or biopsy confirmed Prostate cancer
- Willing and able to provide written informed consent
Key exclusion criteria (5 listed)
- Men who suffer with claustrophobia or are unable to have an MRI e.g. implantable defibrillator, brain aneurysm clips or other implant, severe obesity or unable to lay still for length of scan.
- Men with an impaired renal function (eGFR <30)
- Previous prostate radiotherapy/focal treatment
- Hormonal treatment for prostate cancer within preceding 3 months from consenting to the study.
- Dementia or other neurological condition meaning participant lacks the capacity to consent.
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
ProVal Primary Objective
Time frame: 3 years
To determine the prognostic value of VERDICT metrics for risk classification of patients with early prostate cancer suitable for active surveillance. Quantitive value: fIC (intracellular (IC) volume fraction) among others within model.
ProVal Primary Objective
Time frame: 3 years
To determine the prognostic value of Luminal Index for risk classification of patients with early prostate cancer suitable for active surveillance. Quantitive value: Luminal index
ProVal Primary Objective
Time frame: 3 years
To determine the prognostic value of 13C-HYP-MRI for risk classification of patients with early prostate cancer suitable for active surveillance. Quantitive value: Lactate and pyruvate ratio parameters.
BioVal Primary Objective
Time frame: 3 years
To estimate the association of 13C-HYP-MRI derived quantitative metrics against histological features of prostate cancer. Quantitive value: Lactate and pyruvate ratio parameters.
BioVal Primary Objective
Time frame: 3 years
To estimate the association of 13C-HYP-MRI derived quantitative metrics against histological features of prostate cancer. Quantitive value: Gleason Grade
TecVal Primary Objective
Time frame: 3 years
Inter-site repeatability and intra-site reproducibility of signals derived from VERDICT, Luminal Index MRI and 13C-pyruvate HYP-MRI in men with known prostate cancer. Metric: Repeatability and reproducibility co-efficients
1 secondary outcome
ProVal Secondary Objective
Time frame: 3 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2022.
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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.
Trial Manager contact
Shonit Punwani, MD PhD principal investigator
UCL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer, run by University College, London at 1 site 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 4 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 29 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adam Retter, MD (7398762767 ext. +044, rhmaret@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ProVal Primary Objective (time frame: 3 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jul 2022.