Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prospective Evaluation of Mp-MRI, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Prostate Cancer (PROMM-AS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03979573
Recruitment Status : Recruiting
First Posted : June 7, 2019
Last Update Posted : June 7, 2019
Sponsor:
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf

Brief Summary:

Active Surveillance (AS) is a treatment option in patients with favorable risk prostate cancer. According to the current guidelines patients are monitored by prostate specific antigen (PSA) testing (every 3 months) and regular re-biopsies. Due to histological reclassification and/or patient noncompliance a high number of patients discontinue AS. Nonetheless, because of an increasing number of diagnosed early stage tumors overdiagnosis and overtreatment of patients has become a major clinical problem. Therefore AS is a promising and important tool for patients with low and intermediate risk prostate cancer.

Multiparametric MRI (mp-MRI) in combination with radiomics analysis, MR-guided biopsies, and molecular markers are promising tools to optimize patient selection and observation during AS.

This prospective, single arm, multicenter phase II study evaluates mp-MRI, radiomics, MR-guided biopsies and molecular markers for AS with the primary endpoint of reducing discontinuation based on histologic reclassification.

At the end of this study the results may allow defining a MRI-based pathway to identify and monitor patients suitable for AS supported by radiomics. Thus, the high rate of discontinuation due to misclassification at initial diagnosis will be reduced.

Additionally, this strategy will allow reducing over-treatment of clinically insignificant PCA, and on the other hand, increasing early treatment of higher-risk disease. Monitoring by mp-MRI will reduce the number of prostate biopsies and cores per patient during AS, and thus increase the patient compliance. Finally, such a strategy will reduce the economic burden of treating insignificant prostate cancer.


Condition or disease Intervention/treatment Phase
Prostate Cancer Diagnostic Test: Multiparametric MRI Diagnostic Test: Radiomics Diagnostic Test: MR-guided Biopsy Diagnostic Test: Molecular Markers Not Applicable

Detailed Description:

This prospective multicenter phase II study evaluates multiparametric MRI (mp-MRI), radiomics and MR-guided biopsies for Active Surveillance (AS) of men with low- and intermediate-risk prostate cancer (PCA) with the primary endpoint of reducing the rate of discontinuation of AS based on histologic reclassification in an observation period of 24 months.

Men with low- or intermediate-risk PCA diagnosed by mp-MRI followed by an MR/ultrasound fusion-guided biopsy (FUS-GB) plus systematic ultrasound-guided biopsy (SB) will be included in this study.

During the study observation period PSA values will be obtained every 3 months. After having obtained three values PSA doubling times (PSA-DT) will be calculated at every visit. In case of PSA-DT <3 years patients will get a repeat mp-MRI and in case of MRI progression a repeat targeted FUS-GB plus SB will be performed. In case of a Gleason score upgrading by the targeted biopsy the patient will discontinue AS and get treatment. In cases of stable MRI or stable Gleason score the patient will continue with PSA controls every 3 months.

In addition all patients with stable PSA values will undergo a mp-MRI after 12 months. If this MRI demonstrates progression the protocol proceeds as mentioned above for patients with PSA-increase. At the end of study (24 months after enrollment), all patients will receive another mp-MRI and FUS-GB+SB.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective' Single-Arm, Phase-II Study
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Prospective Phase II Trial Evaluating Multiparametric MRI, Radiomics, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Patients With Low- and Intermediate-Risk Prostate Cancer
Actual Study Start Date : October 1, 2017
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Intervention Arm
  • PSA testing
  • Multiparametric MRI (mp-MRI)
  • Radiomics
  • MR-guided biopsy (MR-guided and systematic US-guided)
  • Molecular Markers (Histological analysis of biopsy cores)
Diagnostic Test: Multiparametric MRI
Multiparametric prostate MRI (mp-MRI)

Diagnostic Test: Radiomics
Radiomics analyses will consist of image intensity normalization, image coregistration and resampling, radiomic feature extraction, combination with clinical and molecular parameters, feature extraction and machine learning, model testing on validation and test cohorts and comparison to existing clinical risk models.

Diagnostic Test: MR-guided Biopsy
MR-guided targeted prostate biopsies as well as systematic TRUS-guided biopsies (at least 12 cores) will be performed on a fusion-guided biopsy system. The biopsy cores can either be obtained transrectal or transperineal.

Diagnostic Test: Molecular Markers
Molecular markers will be analyzed on the initial and final targeted and systematic biopsy cores. The molecular panel consists of a methylation-specific PCR and a set of highly selected markers that can be detected by immunohistochemistry. The resulting data will be prospectively recorded to enable a retrospective analysis of the prognostic value.




Primary Outcome Measures :
  1. Reduction of the discontinuation of Active Surveillance (AS) [ Time Frame: 24 months ]
    Reduction of the discontinuation of AS from 25% to 15% of patients after 24 months based on re-biopsy Gleason score upgrading


Secondary Outcome Measures :
  1. Value of MRI (ADC) regarding aggressiveness [ Time Frame: 36 months ]
    Evaluation of ADC values in s/mm2

  2. Detectionrates of targeted (FUS-GB) versus systematic (TRUS-GB) biopsies [ Time Frame: 36 months ]
    Comparison of detection rates (in %)

  3. Detectionrates of targeted (FUS-GB) versus systematic (TRUS-GB) biopsies [ Time Frame: 36 months ]
    Comparison of Gleason score upgrades (in %) (Gleason score in units 6-10 )

  4. Correlation of clinical parameters with Gleason score progression or MRI quantified progression [ Time Frame: 36 months ]
    Correlation of PSA elevation in ng/ml

  5. Correlation of clinical parameters with Gleason score progression or MRI quantified progression [ Time Frame: 36 months ]
    Correlation of PSA density in ng/ml/ml

  6. Correlation of clinical parameters with Gleason score progression or MRI quantified progression [ Time Frame: 36 months ]
    Correlation of age in years

  7. Patient compliance to recommended MRI-based observation [ Time Frame: 36 months ]
    Number of patients drop outs

  8. Patient compliance to recommended MRI-based observation [ Time Frame: 36 months ]
    Patient discontinuation rate (in %)

  9. Evaluation of Resolve DWI [ Time Frame: 36 months ]
    Improvement of SNR (signal-to-noise ratio)

  10. Evaluation of Resolve DWI [ Time Frame: 36 months ]
    Subjective Image Quality (5-point scale; evaluated by 2 blinded radiologists; total score from 1=non diagnostic, 2=poor, 3=acceptable, 4=good, to 5=excellent)

  11. Evaluation of Resolve DWI [ Time Frame: 36 months ]
    Improvement of tumor detection rate (in %)

  12. Evaluation of Resolve DWI [ Time Frame: 36 months ]
    NPV (in %)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a Gleason score of 3+3=6 or 3+4=7a and ≤ 33% of positive biopsy cores verified by an at least 12 core systematic prostate biopsy (SB)
  • Organ-confined disease (≤cT2a), note: tumor-positive biopsies in both lobes with non-palpable tumor are rated as cT1c
  • PSA value ≤10 ng/ml

Exclusion Criteria:

  • Gleason score ≥4+3=7b or a Gleason score 3+4=7a with positive biopsy cores >33% of all cores in SB
  • PSA >10 ng/ml
  • Patients not able to give informed consent
  • Contraindication to mp-MRI
  • Contraindication to prostate biopsy

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): NCT03979573


Contacts
Layout table for location contacts
Contact: Lars Schimmöller, MD +49 211-81-08505 Lars.Schimmoeller@med.uni-duesseldorf.de
Contact: Christian Arsov, MD +49 211-81-08607 Christian.Arsov@med.uni-duesseldorf.de

Locations
Layout table for location information
Germany
University Düsseldorf, Medical Faculty Recruiting
Dusseldorf, NRW, Germany, 40225
Contact: Almut Diem    +49 211-8119353    diem@med.uni-duesseldorf.de   
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
Investigators
Layout table for investigator information
Principal Investigator: Lars Schimmöller, MD University Düsseldorf, Medical Faculty; Department of Diagnostic and Interventional Radiology
Principal Investigator: Christian Arsov, MD University Düsseldorf, Medical Faculty; Department of Urology

Layout table for additonal information
Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT03979573     History of Changes
Other Study ID Numbers: 5941R
First Posted: June 7, 2019    Key Record Dates
Last Update Posted: June 7, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Heinrich-Heine University, Duesseldorf:
Prospective Study
Multiparametric MRI
Radiomics
MR-guided Biopsy
Molecular Markers
Active Surveillance
Prostate Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases