68Ga-RM2 PET/MRI in Biochemically Recurrent Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
Prostate cancer (PC) remains the most-common non-cutaneous cancer diagnosed in American males, accounting for an estimated 174,560 estimated new cases and 31,620 estimated deaths in 2019. Up to 40% of the patients with prostate cancer develop biochemical recurrence within 10 years after initial treatment. Usually an increase of the prostate-specific antigen (PSA) llevel precedes a clinically detectable recurrence by months to years, and this is currently used as a screening test before and subsequent to treatment. However, disease advancement can be local, regional or systemic, and each has significantly different approaches to disease management. Unfortunately, PSA level does not differentiate between these disease stages. This phase 2-3 study explores the utility of radiolabel 68Ga-RM2, a 68-gallium (68Ga)-labeled gastrin-releasing peptide receptor (GRPr) antagonist, for positron emission tomography (PET) / magnetic resonance imaging (MRI) (collectively, PET/MRI) as a potential tool to help discriminate between disease stages in participants after treatment with surgery or radiation, who present persistently elevated PSA levels (ie, may have prostate cancer), but were negative for cancer with a diagnostic regular medical care computed tomography (CT) scan 68Ga-RM2 (BAY86-7548) is also identified as a synthetic bombesin receptor antagonist. PET/MRI is the collective result of 2 scan processes (PET and MRI ) conducted during the same scan procedure (ie, a combined scan). After a regular medical care computed tomography (CT) scan, participants will be scanned with 68Ga-RM2 PET/MRI scan procedure. PET/MRI is used to assess the location, size, and metabolic activity of a suspected tumor. The 68Ga-RM2 radiolabel consisted of a ligand (the synthetic bombesin receptor antagonist) and the radioisotope 68Ga. The RM2 ligand targets gastrin-releasing peptide receptors (GRPr), commonly expressed by prostate cancer cells, and the radioisotope distinguishes those cells from the background. The criteria for scan positivity will be, when compared to background level of the liver (control), the 68Ga signal is stronger (positive - malignant) or weaker (negative - benign). This study will assess how well 68Ga-RM2 works in detecting prostate cancer in patients with 68Ga-RM2 PET/MRI may be able to see smaller tumors than the standard of care contrast-enhanced CT or MRI scan.

Detailed Description
-----------------
PRIMARY OBJECTIVES: Evaluate 68Ga-RM2 as the radiolabel for PET/MRI scans used for detection of recurrent prostate cancer after initial therapy in patients with elevated prostate-specific antigen (PSA) and non-contributory computed tomography (CT). OUTLINE: Patients receive 68Ga-RM2 intravenously (IV) and beginning 45 minutes later undergoing PET/MRI scan. The 68Ga-RM2 PET/MRI may be repeated at the completion of treatment to evaluate response to therapy, if requested by the treating physician. After completion of study, patients are followed up at 24 to 48 hours and then at 1 year.

Official Title
-----------------
68Ga-RM2 PET/MRI in the Evaluation of Patients With Biochemical Recurrence of Prostate Cancer and Non-contributory CT Scans

Conditions
-----------------
Prostate Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: 68Ga-RM2
* Procedure: Magnetic Resonance Imaging
* Procedure: Positron Emission Tomography


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Biopsy proven prostate adenocarcinoma Rising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy Post radical prostatectomy (RP) - American Urological Association (AUA) recommendation PSA greater than 0.2 ng/mL measured 6-13 weeks after RP Confirmatory persistent PSA greater than 0.2 ng/mL Post-radiation therapy - American Society for Therapeutic Radiology and Oncology (ASTRO)-Phoenix consensus definition Nadir plus (+) greater than or equal to 2 ng/mL rise in PSA No evidence of metastatic disease on conventional imaging, including a negative bone scan for skeletal metastasis and negative contrast-enhanced CT Able to provide written consent Karnofsky performance status of >= 50 (or Eastern Cooperative Oncology Group [ECOG]/World Health Organization [WHO] equivalent) Exclusion Criteria: Unable to provide informed consent Inability to lie still for the entire imaging time Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (severe claustrophobia, radiation phobia, etc.) Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance Metallic implants

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (68Ga-RM2 PET/MRI)<br>Patients receive 68Ga-RM2 IV and beginning 45 minutes later undergoing PET/MRI scan. The 68Ga-RM2 PET/MRI may be repeated at the completion of treatment to evaluate response to therapy, if requested by the treating physician. Imaging with PET/MRI is the intervention. | Drug: 68Ga-RM2<br>* Imaging with PET/MRI<br>* Other names: DOT-bombesin;Procedure: Magnetic Resonance Imaging<br>* Imaging with 68Ga-RM2 PET/MRI<br>* Other names: MRI;Procedure: Positron Emission Tomography<br>* Imaging with 68Ga-RM2 PET/MRI<br>* Other names: PET;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Tumor Lesions Detected by 68Ga-RM2 MRI vs 68Ga-RM2 PET/MRI | Diagnostic performance of 68Ga-RM2 as a contrast imaging label will be assessed by magnetic resonance imaging (MRI) alone, or as a combined scan with positron emission tomography (PET, collectively PET/MRI). The outcome is reported as the number of tumor lesions detected with MRI alone, or with the combination PET/MRI scan, a number without dispersion. | 1 day | 
| Sensitivity of MRI Alone vs PET/MRI | Sensitivity is the ability of a test to correctly identify patients who have the prostate cancer, ie, how well 68Ga-RM2 MRI vs 68Ga-RM2 PET/MRI correctly detects patients who truly have prostate cancer. Sensitivity is defined as [TP/(TP+FN)], where TP=true-positive, and FN=false-negative. The outcome is a percentage number with 95% confidence interval (95% CI). A higher % value means a greater probability that an imaging target identified as cancerous is confirmed by histology to be cancerous, and a lower % means reduced confidence in that result. | 1 day | 
| Specificity of MR Alone vs PET/MRI | Specificity is the ability of a test to correctly identify patients who do not have the prostate cancer, ie, how well 68Ga-RM2 MRI vs 68Ga-RM2 PET/MRI correctly detects patients who do not have prostate cancer (does not falsely return a positive result). Specificity is defined as [TN/(TN+FP)], where TN=true-negative, and FP=false-positive. The outcome is a percentage number with 95% confidence interval (95% CI). A higher % value means a greater probability that an imaging target identified as non-cancerous is confirmed by histology to be non-cancerous, and a lower % means reduced confidence in that result. | 1 day |