IGPC-5: Multi-modality Imaging (PCa) Using Sodium MRI and PSMA PET in Men Pre-prostatectomy

Sponsor

Glenn Bauman (Other)

Overall Status

Recruiting

CT.gov ID

NCT04053842

Collaborator

University of Western Ontario, Canada (Other), United States Department of Defense (U.S. Fed), Centre for Probe Development and Commercialization (Other)

Enrollment

Location

Arm

18.9

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is a non-randomized, prospective trial of men scheduled for radical prostatectomy for treatment of prostate cancer as standard of care and will undergo a series of pre-operative multi-modality imaging studies. Pre-operative imaging will be correlated with actual pathology results and statistical modeling performed to determine the most informative imaging biomarkers in predicting cancer location and aggressiveness (Gleason Score).

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Prostate Adenocarcinoma Prostate Neoplasm	Diagnostic Test: PET Scan Drug: [F-18]-DCFPyL Injection Diagnostic Test: Sodium MRI Diagnostic Test: Multiparametric MRI	Phase 2

Detailed Description

The over-arching goal is to "improve the quality of life for survivors of prostate cancer" through advanced imaging tools for improved pre-treatment detection and characterization of prostate cancer through non-invasive imaging.

Seminal research measuring tissue sodium concentration (TSC) in human PCa with sodium MRI has demonstrated increased TSC in prostate lesions related to tumor aggressiveness. This suggests that the addition of sodium MRI to mpMRI data will enhance the identification and characterization of prostate lesions in men with PCa. This will improve the healthcare of men through better risk stratification and treatment decisions, which will ultimately reduce overtreatment. Radio-labeled PET tracers that target PSMA have demonstrated exceptional sensitivity for molecular imaging of prostate lesions. Lesion-detection specificity of combined PSMA PET and mpMRI is very high (97 - 100%). However, PSMA PET is not practical for active surveillance of prostate cancer within the current healthcare system due to limited access and the fact that its added cost and radiation dose restricts its utility for repeated scans. However, as a tool to develop and validate our imaging assay, it is unparalleled. Compared with hybrid PET/MRI, a single modality imaging assay based only on mpMRI contrasts and endogenous TSC would be more widely available, cost effective and find wider clinical adoption - particularly for AS. The immediate expected outcome from this project is that an MRI assay combining data from mpMRI and sodium MRI will have a similar ability as PSMA PET to accurately discriminate between low- and high-risk PCa for improved treatment decisions and surveillance of low-risk disease.

The transformative potential of a non-invasive, single modality, whole-gland imaging assay comprised of biomarkers from combined TSC and mpMRI could ultimately replace serial biopsies for surveillance of men with low- and intermediate-risk disease. Patients who are educated to understand the typical slow progression of low-risk PCa, surveillance methods and treatment risks are more likely to consider AS. In a systematic approach developed to improve physician counselling of low-risk PCa patients, the acceptance rate for AS was improved to 94% - a relative reduction of approximately 30% in the risk of unnecessary curative treatment. However, it is also important to note that the rate of subsequent treatment for men undergoing AS may be as high as 50% over 10 years of follow-up. The majority of these men are transitioned to treatment within 2-3 years of initial diagnosis. Identification of those men who fit the criteria for AS but are destined to have early progression is an important clinical goal. Those men can be streamed to early treatment through longitudinal assessment of lesion progression with this imaging assay and thus increase the confidence and uptake of AS protocols. AS of PCa (including possible delayed treatment) saves costs over the lifetime of a patient, compared with immediate treatment and provides superior quality of life.

Research Strategy: The investigators will evaluate a non-invasive imaging assay for in vivo characterization of prostate lesions comprised of clinical multi-parametric magnetic resonance imaging (mpMRI) combined with sodium magnetic resonance imaging (sodium MRI) in a cohort of men with biopsy-proven prostate cancer. The use of mpMRI to detect, localize and stage prostate cancer is becoming standard clinical practice. Prior research in ten patients has established that tissue sodium concentration (TSC) assessed by sodium MRI increases significantly with histological grade in prostate lesions. The addition of TSC data to conventional mpMRI data (i.e. ADC values, T2 contrast, contrast agent wash-in/out rates) will be evaluated in a multivariate data analysis to demonstrate that a combination of these imaging protocols improves the characterization of PCa. The resulting predictive tool (imaging assay) will accurately discriminate between low- and high-risk PCa for improved treatment decisions and to assess possible progression of low-risk disease during surveillance.

This imaging assay will be validated against positron emission tomography (PET) using a radio-labeled tracer which binds to prostate-specific membrane antigen (PSMA). PSMA PET is arguably the most sensitive imaging method for detection of intra-prostatic lesions. Importantly, it has a high sensitivity for prostate lesion detection (>90%), even for lower tumor grades where mpMRI has difficulties. Maximum standard uptake value (SUVmax) of this radiotracer has been positively correlated with Gleason grade and as such, is an excellent comparator for TSC assessment of lesion aggressiveness. Unfortunately, the limited accessibility and cost of PET hinders its clinical application.

In this project, the investigators expect to validate that the addition of sodium MRI to mpMRI can provide similar lesion characterization compared to PSMA PET. Data supporting this hypothesis will be acquired using a hybrid PET/MRI system because this is the best imaging platform for this project. If successful, the incorporation of sodium MRI into existing mpMRI protocols would improve characterization of disease and be a more cost effective and generalizable innovation compared to PET-based techniques that require both an expensive probe as well as hybrid imaging platforms.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Multi-modality Prostate Cancer Image Guided Interventions - 5

Actual Study Start Date :

Feb 4, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multi-modality prostate cancer imaging The study requires eligible patients to complete one imaging session at St. Joseph's Health Care to begin within 6 weeks of the scheduled Radical Prostatectomy. Imaging will consist of simultaneous multiparametric MRI (mpMRI), sodium MRI and positron emission tomography (PET) with a radio-labeled probe for prostate-specific membrane antigen (PSMA).	Diagnostic Test: PET Scan PET imaging uses small amounts of a radioactive substance called a tracer to look for disease in the body. The radioactive substance used in this study is [F-18]-DCFPyL. Other Names: PSMA PET Drug: [F-18]-DCFPyL Injection [F-18]-DCFPyL is given by intravenous (IV) injection into the arm. It travels through the blood stream where it is rapidly taken up by prostate cancer cells and emits tiny, positively charged particles (called positrons) that produce signals into the body. These signals are detected by the PET component of the PET/MRI scanner. Other Names: PSMA Diagnostic Test: Sodium MRI Sodium MRI uses magnetic waves and a specially-designed rectal probe to measure the sodium concentration (amount of salt) in the prostate. Previous research has shown that higher sodium concentrations in the prostate might be a sign of more aggressive cancer. Diagnostic Test: Multiparametric MRI MRI is a common medical diagnostic tool that uses magnetic waves and a contrast agent (dye) called Gadovist to take pictures of body tissue. Other Names: mpMRI

Arm

Intervention/Treatment

Experimental: Multi-modality prostate cancer imaging

The study requires eligible patients to complete one imaging session at St. Joseph's Health Care to begin within 6 weeks of the scheduled Radical Prostatectomy. Imaging will consist of simultaneous multiparametric MRI (mpMRI), sodium MRI and positron emission tomography (PET) with a radio-labeled probe for prostate-specific membrane antigen (PSMA).

Diagnostic Test: PET Scan

PET imaging uses small amounts of a radioactive substance called a tracer to look for disease in the body. The radioactive substance used in this study is [F-18]-DCFPyL.

Other Names:

PSMA PET

Drug: [F-18]-DCFPyL Injection

[F-18]-DCFPyL is given by intravenous (IV) injection into the arm. It travels through the blood stream where it is rapidly taken up by prostate cancer cells and emits tiny, positively charged particles (called positrons) that produce signals into the body. These signals are detected by the PET component of the PET/MRI scanner.

Other Names:

PSMA

Diagnostic Test: Sodium MRI

Sodium MRI uses magnetic waves and a specially-designed rectal probe to measure the sodium concentration (amount of salt) in the prostate. Previous research has shown that higher sodium concentrations in the prostate might be a sign of more aggressive cancer.

Diagnostic Test: Multiparametric MRI

MRI is a common medical diagnostic tool that uses magnetic waves and a contrast agent (dye) called Gadovist to take pictures of body tissue.

Other Names:

mpMRI

Outcome Measures

Primary Outcome Measures

Pathologic Validation and Modeling [4 years]
We will evaluate the ability of simultaneous multiparametric MRI (mpMRI), sodium MRI and positron emission tomography (PET) with a radio-labeled probe for prostate-specific membrane antigen (PSMA) to accurately predict the actual cancer distribution found in the whole mount prostatectomy specimens obtained from the surgery. A variety of statistical methods will be utilized to build predictive models based on the extracted features and to identify a final model that will be used as the predictive tool (i.e. the imaging assay). We will quantify the ability of these models to enhance clinical lesion identification.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of informed consent for this study
Male, aged 18 years or older
Pathologically confirmed prostate cancer on previous biopsy
Suitable for and consenting to Radical Prostatectomy for treatment as standard of care

Exclusion Criteria:

Prior therapy for prostate cancer (including hormone therapy)
Use of 5-alpha reductase inhibitors, i.e. finasteride (Proscar) or dutasteride (Avodart) within 6 months of study start. Patients undergoing a 6-month washout period prior to study start will be eligible.
Inability to comply with the pre-operative imaging panel
Patients scheduled for radical prostatectomy with prostate size exceeding 65 cc
Allergy to contrast agents to be used as part of the imaging panel
Acute kidney injury (AKI), chronic kidney disease (CKD) Stage 4 or 5 (estimated Glomerular Filtration Rate [eGFR] < 30 mL/min/1.73m2) or those on dialysis
Post-void residual urine volume > 150 cc (determined by post-void ultrasound)
Hip prosthesis, vascular grafting that is MRI incompatible or sources of artefact within the pelvis
Contraindication to MRI
pacemaker or other electronic implants
known metal in the orbit
cerebral aneurysm clips