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Comparison of Diagnostic Accuracy of Luminal Index and MP MRI for Accelerated deTEction of Significant Prostate Cancer (CLIMATE)

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ClinicalTrials.gov Identifier: NCT05020522
Recruitment Status : Recruiting
First Posted : August 25, 2021
Last Update Posted : May 26, 2022
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief Summary:

Multi-parametric (mp) MRI has now internationally been incorporated as standard of care in the work-up of participants with suspected prostate cancer. The standard mpMRI protocol requires 30-45 minutes to be performed and has a sensitivity and specificity of approximately 90% and 50% for the detection of clinically significant prostate cancer. Compared to the non-targeted systematic transrectal ultrasound (TRUS) biopsy approach in men with clinically suspected prostate cancer (e.g.: elevated PSA), performing mpMRI as a triage test allows to detect clinically significant cancer in more men (38% vs 26%) and clinically insignificant cancer in less men (9% vs 22%), while avoiding biopsy in roughly one third of men.

However, there is need for improvement in the prostate diagnostic pathway even after incorporation of mp-MRI, specifically mpMRI can miss significant cancer in around 10% of cases and only 50% of positive scans turn out to harbor significant cancer at biopsy. Moreover, the key functional imaging sequence of mp-MRI (i.e.: DWI) often suffers from image artifacts causing difficulty in scan interpretation.

To address these issues the investigators aim to investigate Luminal Index MRI (LI-MRI), a novel method of MR imaging that requires only up to 10 minutes to be performed and doesn't require the use of contrast media. LI-MRI has shown promising results for the characterization of prostate cancer.

In this study the diagnostic performance of LI-MRI and mpMRI for the detection of prostate cancer will be directly compared.


Condition or disease Intervention/treatment Phase
Prostate Cancer Diagnostic Test: Luminal Index MRI (LI-MRI) Diagnostic Test: LI-MRI targeted prostate biopsy Diagnostic Test: Plasma methylation signature (ctMethSig) Not Applicable

Detailed Description:

Luminal Index MRI (LI-MRI). LI-MRI is a novel technique that allows the assessment of luminal water fraction (LWF). The normal prostate consists of a glandular lumen and cellular areas; cancer alters the balance of glandular to cellular spaces, reducing the fraction of glandular lumen. This fraction decreases further as the grade of tumor increases. Using a multiecho T2-weighted sequence, investigators can differentiate between long T2 values of the luminal space and the short T2 values of the stromal/epithelial space. The luminal index of an image pixel can be calculated as a fraction of the area of the luminal space to the sum of cellular-stromal and luminal space. Studies have shown a good correlation between LWF and its histological measurement, with potential to detect prostate cancer and predict tumor grade. From the results of preliminary studies, the optimized LI-MRI sequence has been very good at differentiating clinically significant and non-significant tumors.

PURPOSE. The purpose of the study is to compare the diagnostic performance of LI-MRI (up to 10 minutes scan, no contrast required) and mp-MRI (35-40 min scan, intravenous contrast injection required) for the detection of clinically significant prostate cancer.

DESIGN. This is a prospective, multi-centre, paired, non-randomised, comparative study. Patients with clinically suspected prostate cancer that are scheduled for mpMRI as part of their routine diagnostic workup will be asked to participate to the study. All participants will undergo an additional LI-MRI sequence during the clinical scan session. Mp-MRI and LI-MRI images will be interpreted independently by different radiologists, blinded to the results of the other test. Targeted biopsies will be performed for any suspicious lesion (i.e. MRI score 3-4-5) detected with mpMRI and/or LI-MRI, blinded to the source of the lesion. The diagnostic performance of the two techniques will then be assessed using the results of the targeted biopsy.

An optional translational study will also be performed to investigate the ability of DNA methylation signatures in the plasma to identify men at high risk of metastases from high risk prostate cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 702 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Paired, non-randomised, comparative study
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Comparison of the Diagnostic Accuracy of Luminal Index Magnetic Resonance Imaging and Multi-parametric Magnetic Resonance Imaging for the Accelerated Detection of Significant Prostate Cancer
Actual Study Start Date : May 1, 2022
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : March 1, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
MRI scan
Mp-MRI, LI-MRI, plasma DNA methylation signature (optional)
Diagnostic Test: Luminal Index MRI (LI-MRI)
Multiecho T2 sequence; eventual biopsy of lesion(s) detected with LI-MRI only.

Diagnostic Test: LI-MRI targeted prostate biopsy
Biopsy targeted to suspicious lesions detected with LI-MRI only

Diagnostic Test: Plasma methylation signature (ctMethSig)
Blood sample.




Primary Outcome Measures :
  1. Diagnostic accuracy of mp-MRI and LI-MRI [ Time Frame: 3 years ]
    Comparison of per-participant diagnostic accuracy of mp-MRI and LI-MRI for the detection of clinically significant prostate cancer (i.e. Gleason 3+4 or higher). Two endpoints are included in the primary outcome: difference in sensitivity and difference in specificity.


Secondary Outcome Measures :
  1. Diagnostic accuracy of LI-MRI as an add-on test [ Time Frame: 3 years ]
    Per-participant diagnostic accuracy of LI-MRI as an add-on test in combination with mp-MRI for the detection of clinically significant cancer.

  2. Proportion of correct clinical recommendation [ Time Frame: 3 years ]
    Comparison of the proportion of men who would receive a correct clinical recommendation that biopsy could be avoided using mp-MRI and LI-MRI by retrospective analysis.

  3. Per-lesion diagnostic accuracy of mp-MRI and LI-MRI [ Time Frame: 3 years ]
    Comparison of per-lesion diagnostic accuracy of LI-MRI and mp-MRI for clinically significant cancer (difference in sensitivity and specificity).

  4. Proportion of non-significant cancer detection [ Time Frame: 3 years ]
    Comparison of the proportion of men diagnosed with non-significant cancer (Gleason 3+3) based on LI-MRI and mp-MRI targeted biopsies.

  5. Value of MRI in diagnostic models [ Time Frame: 3 years ]
    Evaluation of the added value of MRI when included in a diagnostic model of clinically significant cancer based on the clinical features of age and PSA density.

  6. Luminal Index quantitative analysis [ Time Frame: 3 years ]
    Correlation between Luminal Index quantitative metric and tumor Gleason grade

  7. Interobserver agreement on LI-MRI scores [ Time Frame: 3 years ]
    Interobserver agreement among radiologists on LI-MRI scores.

  8. Interobserver agreement on Gleason scores [ Time Frame: 3 years ]
    Interobserver agreement among histopathologists on Gleason scores at biopsy.

  9. ctMethSig true positive rate [ Time Frame: 3 years ]
    Proportion of men with clinically significant cancer who are positive with ctMethSig.

  10. ctMethSig false positive rate [ Time Frame: 3 years ]
    Proportion of men without clinically significant cancer who are positive with ctMethSig.


Other Outcome Measures:
  1. ctMethSig and risk of metastases [ Time Frame: 3 years ]
    Correlation of ctMethSig with other clinical factors known to be associated with risk of metastasis (e.g. Gleason grade)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men with clinically suspected prostate cancer and referred for prostate MRI
  • Willing and able to provide a written informed consent

Exclusion Criteria:

  • Prostate specific antigen (PSA) level > 20ng/ml within 6 months
  • Previous diagnosis of prostate cancer
  • Ongoing hormone treatment within 3 months prior to MRI, excluding antiandrogens or 5-alpha reductase inhibitors
  • Contraindication to MRI scan
  • Contraindication to administration of gadolinium-based contrast agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05020522


Contacts
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Contact: Nicola Muirhead, PhD 02076795279 ncita.climate@ucl.ac.uk

Locations
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United Kingdom
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Shonit Punwani         
Sponsors and Collaborators
University College, London
Investigators
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Principal Investigator: Shonit Punwani University College, London
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT05020522    
Other Study ID Numbers: 281621
First Posted: August 25, 2021    Key Record Dates
Last Update Posted: May 26, 2022
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University College, London:
Magnetic Resonance Imaging
Luminal Index MRI
Methylation Signature
Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Phenobarbital
Anticonvulsants
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
GABA Agents
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers