11C- and 18F-Choline PET/MR Imaging for Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well 11C-choline (carbon C 11 choline) and 18F-choline (fluorine F 18 choline) positron emission tomography/magnetic resonance (PET/MR) imaging works in diagnosing patients with unfavorable intermediate to high-risk prostate cancer. Diagnostic procedures, such as 11C- and 18F-choline PET/MR may help find and diagnose prostate cancer and find out how far the disease has spread.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To assess the ability of 11C- and 18F-choline PET/MR to detect and localize prostate cancer within the prostate gland. SECONDARY OBJECTIVES: I. To assess the ability of 11C- and 18F-choline PET/MR to detect the specific location of metastatic prostate cancer within pelvic lymph node regions in patients undergoing radical prostatectomy and extended pelvic lymph node dissection. II. To assess the comparative performance of 11C- and 18F-choline PET/MR to already available imaging scans (bone scan, sodium fluoride positron emission tomography/computed tomography [NaF PET/CT], multiparametric1H magnetic resonance imaging [MRI], and/or pelvic CT scans) for detecting and localization of disease within the prostate, lymph nodes, and distant metastatic sites. III. To determine the temporal distribution of 11C- and 18F-choline radiotracer in patients. The tissue uptake, retention, and clearance will be determined. EXPLORATORY OBJECTIVES: I. To compare regions of uptake on the 11C- and 18F-choline PET/MR to that on the sentinel lymph node imaging scans in patients undergoing sentinel lymph node-guided extended pelvic lymph node dissection. OUTLINE: Patients undergo 11C- and 18F-choline whole-body PET/MR imaging. After completion of study treatment, patients are followed up for 3 hours

Official Title
-----------------
Phase 2 Study of 11C- and 18F-Choline PET/MR Imaging in Patients With Unfavorable Intermediate to High-Risk Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Carbon C 11 Choline
* Drug: Fluorine F 18 Choline
* Procedure: Positron Emission Tomography (PET) / Magnetic Resonance Imaging (MRI)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: Patients must be >=18 years of age Diagnosis: Patients must have a diagnosis of prostate cancer by histologic verification and a hypoechoic lesion seen on ultrasound. Disease Status: Unfavorable intermediate to high-risk prostate cancer, per the Cancer of the Prostate Risk Assessment Score (CAPRA) (CAPRA 5-10) Karnofsky Performance Status >=70 Metastatic workup: Whole Body Sodium Fluoride (NaF) PET/CT or 99mTc Bone Scan Planned to undergo radical prostatectomy and extended pelvic lymph node dissection Adequate bone marrow and organ function defined as follows: Adequate bone marrow function: Leukocytes >= 3,000/microliter (mcL) Absolute Neutrophil Count >= 1,500/mcL Platelets >= 100,000/mcL Adequate hepatic function: Total bilirubin - within normal institutional limits Aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT) <= 2.5 X institutional upper limit of normal Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <= 2.5 X institutional upper limit of normal Adequate renal function: Creatinine - within normal institutional limits OR Creatinine clearance >= 60 mL/min/ 1.73m2 for patients with creatinine levels above institutional normal Ability to understand a written informed consent document, and the willingness to sign it Exclusion Criteria: Participation would significantly delay the scheduled standard of care therapy Karnofsky performance status of < 60 Inadequate venous access Administered a radioisotope within 5 physical half lives prior to study enrollment Have a medical condition or other circumstances which, in the opinion of the investigator would significantly decrease the chances of obtaining reliable data, achieving the study objectives, or completing the study.

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

Sexes Eligible for Study
-----------------
All

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 11C- and 18F-choline PET/MR imaging<br>Patients are given 370 megabecquerel (MBq) 11C-Choline (11C) intravenously and 3 MBq/kg 18F-Choline (18F) intravenously prior to a whole-body PET/MR imaging | Drug: Carbon C 11 Choline<br>* Given intravenously (IV) prior to imaging<br>* Other names: Ethanaminium, 2-hydroxy-N,N-dimethyl-N-(methyl-11C)-;Drug: Fluorine F 18 Choline<br>* Given intravenously (IV) prior to imaging<br>* Other names: [18F]-Choline;Procedure: Positron Emission Tomography (PET) / Magnetic Resonance Imaging (MRI)<br>* Undergo whole-body PET/MR imaging<br>* Other names: Whole-body PET/MR imaging;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Kinetic Parameters Reflecting Fluorocholine (FCH) Fluorine 18 FCH (F-18) Influx (K1) | The average K1 values of primary tumors will be reported along with the standard deviation | Day 1 | 
| Mean Maximum Kinetic Parameters Reflecting F-18 Influx (K1max) | The K1max values of primary tumors will be reported along with the standard deviation | Day 1 | 
| Average Standardized Uptake Value (SUVavg) | The SUVavg values of primary tumors will be reported along with the standard deviation. Typically, a standardized uptake value (SUV), a quantity that incorporates the patient's size and the injected dose, that is more than 2.0 is considered to be suggestive of malignancy | Day 1 | 
| Mean of the Standardized Uptake Value (SUVmax) | The SUVmax values of primary tumors will be reported along with the standard deviation. Typically, a standardized uptake value (SUV), a quantity that incorporates the patient's size and the injected dose, that is more than 2.0 is considered to be suggestive of malignancy. | Day 1 | 
| Sensitivity of Combined Positron Emission Tomography (PET) and Magnetic Resonance (MR) Imaging | Sensitivity (True Positive Rate, TPR) measures the ability of a 11C- and 18F-Choline PET/MR Imaging for Prostate Cancer to correctly identify patient status as respectively diseased or non-dis- eased and is reported as a percentage ranging from 0 -100 with higher percentages indicating a higher sensitivity to identify the prostate cancer using SUVmax . The sensitivity of the combined PET and MR imaging for prediction of pathologic extraprostatic extension will be reported. | Day 1 | 
| Specificity of of Combined Positron Emission Tomography (PET) and Magnetic Resonance (MR) Imaging | Specificity (True Negative Rate) measures the ability of a 11C- and 18F-Choline PET/MR Imaging for Prostate Cancer to correctly identify patient status as respectively diseased or non-dis- eased and is reported as a percentage ranging from 0 -100 with higher percentages indicating a higher specificity to identify the prostate cancer using SUVmax. The specificity of the combined PET and MR imaging for prediction of pathologic extraprostatic extension will be reported. | Day 1 | 
| Correlation of K1 of Primary Tumors With K1max | A spearman rank correlation test was performed to test the correlation of K1 with K1max. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | Day 1 | 
| Correlation of K1 of Primary Tumors With Average Standardized Uptake Value (SUVavg) | A spearman rank correlation test was performed to test the correlation of K1 with the SUVavg of primary tumors. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | Day 1 | 
| Correlation of K1max of Primary Tumors With SUVmax | A spearman rank correlation test was performed to test the correlation of K1max with SUVmax. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | Day 1 | 
| Correlation of K1max of Primary Tumors With SUVavg | A spearman rank correlation test was performed to test the correlation of K1max with SUVavg. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | Day 1 | 
| Correlation of SUVmax of Primary Tumors With SUVavg | A spearman rank correlation test was performed to test the correlation of SUVmax with SUVavg. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of SUVmax of Primary Tumors With Serum Prostate-specific Antigen (PSA) Level | A spearman rank correlation test was performed to test the correlation of SUVmax with a patients baseline PSA. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | Day 1 | 
| Correlation of SUVmax of Primary Tumors With Pathological Stage | The system of pathological staging is developed by the American Joint Committee on Cancer (AJCC) and is divided into 5 stages: stage 0 (zero) and stages I through IV (1 through 4). A spearman rank correlation test was performed to test the correlation of SUVmax with a patient's baseline pathological stage. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | Day 1 | 
| Correlation of SUVmax of Primary Tumors With Post-surgical Cancer of the Prostate Risk Assessment (CAPRA) Scores | The CAPRA is a 5 item questionnaire completed by the clinicians with a total score range from 0-10 calculated using points assigned to: age at diagnosis, PSA at diagnosis, Gleason score of the biopsy, clinical stage and percent of biopsy cores involved with cancer. A CAPRA score of 0 to 2 indicates low-risk, a score of 3 to 5 indicates intermediate-risk, and a score of 6 to 10 indicates high-risk. A spearman rank correlation test was performed to test the correlation of SUVmax with a patient's CAPRA score after surgery. Spearman's correlation coefficient (ρ) determines the strength and direction of the monotonic relationship between two variables. The Spearman correlation coefficient is reported in values from +1 to -1. A ρ= +1 indicates a perfect association of ranks, a ρ = zero indicates no association between ranks and a ρ = -1 indicates a perfect negative association of ranks. The closer ρ is to zero, the weaker the association between the ranks. | After surgery, Up to 6 months | 
| Comparison of SUVmax of Primary Tumors With Post-surgical Cancer of the Prostate Risk Assessment (CAPRA) Score Groups | The CAPRA is a 5 item questionnaire completed by the clinicians with a total score range from 0-10 calculated using points assigned to: age at diagnosis, PSA at diagnosis, Gleason score of the biopsy, clinical stage and percent of biopsy cores involved with cancer. A CAPRA score of 0 to 2 indicates low-risk, a score of 3 to 5 indicates intermediate-risk, and a score of 6 to 10 indicates high-risk. A Mann-Whitney U test was performed to compare the SUVmax with patients classified as intermediate-risk and high risk based on their CAPRA Score. Means and standard deviations will be reported. | After surgery, Up to 6 months |