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High Resolution MRI Study for Prostate Cancer

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03292874
Recruitment Status : Completed
First Posted : September 26, 2017
Results First Posted : April 3, 2024
Last Update Posted : April 3, 2024
Sponsor:
Information provided by (Responsible Party):
Hyung L. Kim, MD, Cedars-Sinai Medical Center

Tracking Information
First Submitted Date  ICMJE September 21, 2017
First Posted Date  ICMJE September 26, 2017
Results First Submitted Date  ICMJE December 13, 2023
Results First Posted Date  ICMJE April 3, 2024
Last Update Posted Date April 3, 2024
Actual Study Start Date  ICMJE September 13, 2017
Actual Primary Completion Date December 14, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2024)
  • Sensitivity and Specificity of High Resolution Versus Standard MRI in Identifying Adverse Histology [ Time Frame: 6-12 months after enrollment ]
    The primary endpoint of the clinical trial was the presence of adverse histology (AH) on prostate biopsy. We defined adverse histology (AH) as either overall Gleason score of 7 or more on any biopsy, or an increase of 3 or more positive cores on serial systematic biopsies. The primary hypothesis was that change in tumor size or apparent diffusion coefficient (ADC) as detected by high resolution MRI (hrMRI) would better predict AH than standard MRI (sMRI). AH histology was a measure intended to capture patients with high Gleason grade component (i.e. Gleason Grade 4 or 5) and patients progressing (e.g. from Gleason Group 1 to Gleason Group 2 or from Gleason Group 2 to Gleason Group 3). The sample size was too small and the followup duration of approximately 12 months was too short to assess only true cancer progression as the endpoint. The presence of AH alone is clinically important since these patients may need close followup and may consider definitive local therapy.
  • Area Under the Receiver Operator Curve of High Resolution Versus Standard MRI in Identifying Adverse Histology [ Time Frame: 6-12 months after enrollment ]
    The primary endpoint of the clinical trial was the presence of adverse histology (AH) on prostate biopsy. We defined adverse histology (AH) as either overall Gleason score of 7 or more on any biopsy, or an increase of 3 or more positive cores on serial systematic biopsies. The primary hypothesis was that change in tumor size or apparent diffusion coefficient (ADC) as detected by high resolution MRI (hrMRI) would better predict AH than standard MRI (sMRI). AH histology was a measure intended to capture patients with high Gleason grade component (i.e. Gleason Grade 4 or 5) and patients progressing (e.g. from Gleason Group 1 to Gleason Group 2 or from Gleason Group 2 to Gleason Group 3). The sample size was too small and the followup duration of approximately 12 months was too short to assess only true cancer progression as the endpoint. The presence of AH alone is clinically important since these patients may need close followup and may consider definitive local therapy.
Original Primary Outcome Measures  ICMJE
 (submitted: September 22, 2017)
Evidence of prostate cancer disease progression [ Time Frame: 3 years from baseline imaging ]
evidence of disease progression as defined by any of the following:
  • Increase in Gleason score from 3 + 3 to Gleason sum 7 on biopsy
  • Gleason score 4+3 on biopsy
  • Gleason sum 8-10 on biopsy
  • > 3 Increase in number of positive cores
  • Progression to nodal or bone involvement
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE High Resolution MRI Study for Prostate Cancer
Official Title  ICMJE Evaluation of a Novel High-Resolution Diffusion-Weighted MRI Sequence
Brief Summary This high resolution MRI (hrMRI), along with stand MRI (sMRI) will be obtained at baseline and again in approximately 1 year in patients on prostate cancer active surveillance. Changes in lesion size and ADC values will be assessed on the serial studies. This study evaluates the hypothesis that hrMRI will detect changes that sMRI cannot detect and that these changes will correlate with prostate cancer progression as determined on prostate biopsy.
Detailed Description

2.0 BACKGROUND AND RATIONALE

Multiparametric MRI Multiparametric MRI combining T2-weighted, diffusion-weighted, and dynamic contrast enhanced (DCE) images is commonly employed for detection and localization of prostate lesions. Diffusion-weighted imaging (DWI) is sensitive to the diffusion of water molecules interacting with surrounding macromolecules. DWI, which provides a quantitative biological parameter called apparent diffusion coefficient (ADC) value, is a robust MRI parameter for differentiating benign and malignant prostate tissue. In fact, the latest version of the Prostate Imaging-Reporting and Data System (PI-RADS) scoring system relies almost exclusively on DWI to identify tumors in the peripheral zone, which is where the vast majority of prostate cancers form. Findings on T2 images are not used to identify cancer, and DCE images are only used to differentiate between some PI-RADS 3 and 4 lesions. In a pilot study of prostate cancer AS, DW-MRI was useful for detecting progression of Gleason score based on changes in ADC value. Tumor size is another important clinical criterion for defining low risk prostate cancer, and tumor size based on DWI has been shown to crudely predict low risk prostate cancer. However, conventional DWI using single-shot echo-planar imaging is unable to detect small tumors, low grade tumors, or small changes in tumor size on serial imaging. Approximately 20% of small, low grade tumors found in men on AS are detected on modern prostate MRI.

High Resolution MRI Investigators introduce a new three-dimensional (3D) high-resolution diffusion-weighted imaging sequence (HR-DWI), which improves image quality while conferring at least a 5-fold improvement in resolution when compared to standard two-dimensional (2D) DWI (S-DWI). This novel 3D DWI technique has been developed by our team and can be applied on existing 1.5T or 3T MRI systems. S-DWI suffers from two important limitations. a) It uses single-shot echo-planar imaging (EPI) for data acquisition, which produces magnetic susceptibility induced streaking artifacts and geometric distortions so that round objects may appear oval. b) The relatively low signal-to-noise ratio and 2D image acquisition with S-DWI limit spatial resolution, which is defined by the minimum distance between two objects required to resolve them uniquely. Our HR-DWI overcomes these limitations by using magnetization prepared, multi-shot, turbo-spin-echo acquisition, which improves signal-to-noise ratio (SNR), spatial resolution, and image quality, and eliminates geometric distortions and streaking artifacts associated with EPI.

Preliminary studies

In preliminary studies assessing the performance of our HR-DWI in a prospective pilot trial of prostate cancer AS patients, the technique could detect tumors not seen on S-DWI and measure ADC, which correlates with grade. This is important because the long-term natural history of small prostate cancers invisible to S-DWI has never been prospectively defined, in part due to lack of adequate imaging technology. In the era of molecular diagnostics and next-generation sequencing, an important step in understanding the biology of these lesions is to develop technologies to image and characterize these lesions. Importance of HR-DWI includes:

  • Better imaging will allow these lesions to be monitored serially and targeted for biopsy, providing tissue for both histologic and molecular characterization.
  • Higher resolution imaging will better delineate tumor boundaries, which can improve tumor staging and identify margins during partial-gland ablation by cryotherapy or high intensity focused ultrasound (HIFU), which was approved in 2015 by the U.S. FDA.
  • Improved imaging resolution will allow for more accurate measurement of tumor size and ADC, and detection of small changes in size or grade over time. Standard prostate DWI has poor resolution; therefore, tumor growth kinetics have never been accepted as clinical criteria for cancer progression while on AS. If tumor growth kinetics or changes in grade determined by ADC prove prognostic, AS can rely less on serial transrectal biopsies, which can lead to serious complications.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single arm, paired imaging
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Prostate Cancer
Intervention  ICMJE Diagnostic Test: high resolution MRI (hrMRI)
high resolution MRI (hrMRI) and standard MRI (sMRI) will be obtained at baseline and again in approximately 1 year in patients on prostate cancer active surveillance.
Study Arms  ICMJE Paired imaging
Single arm, paired imaging of high resolution MRI (hrMRI) and stand MRI (sMRI)
Intervention: Diagnostic Test: high resolution MRI (hrMRI)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 13, 2023)
64
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2017)
59
Actual Study Completion Date  ICMJE December 14, 2022
Actual Primary Completion Date December 14, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age over 18 years
  • Patients diagnosed with clinically localized prostate cancer
  • Low or Low-intermediate Risk Prostate cancer1 defined as:
  • Pre-operative prostate specific antigen (PSA) ≤ 20.0 ng/ml
  • Clinical stage cT1 or cT2
  • Gleason score 3+3 or 3+4
  • Patients choosing AS or already on AS as primary management strategy
  • No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal therapy
  • No contraindications for gadolinium enhanced MRI

Exclusion Criteria:

  • No exclusion criteria
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03292874
Other Study ID Numbers  ICMJE Pro00049177
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hyung L. Kim, MD, Cedars-Sinai Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Cedars-Sinai Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hyung L Kim, MD Cedars-Sinai Medical Center
PRS Account Cedars-Sinai Medical Center
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP