NaF/FDG PET/MRI in Measuring Response to Radium Ra 223 Dichloride in Patients With Metastatic Hormone-Resistant Prostate Cancer

Study Overview
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Brief Summary
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This pilot clinical trial studies combined fluorine F 18 sodium fluoride (NaF)/ fludeoxyglucose F 18 (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) in measuring response to a drug, radium Ra 223 dichloride (Ra-223), in treating patients with prostate cancer that has not responded to hormone therapy and has spread to other parts of the body. Combining NaF/FDG in a simultaneous PET/MRI scan may help doctors accurately measure how well patients respond to treatment with radium Ra 223 dichloride.

Detailed Description
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PRIMARY OBJECTIVES: I. Estimate the performance of simultaneous NaF/FDG PET/MRI for the prediction of treatment response in patients with metastatic castrate resistant prostate cancer (mCRPC). II. Estimate the performance of simultaneous NaF/FDG PET/MRI for detection of extra-skeletal disease progression during treatment in mCRPC patients. OUTLINE: Patients receive 18F NaF and 18F FDG intravenously (IV) over 30 seconds-1 minute and then undergo PET/MRI and contrast-enhanced MRI after 45-60 minutes. Patients undergo imaging at baseline, after course 3 (12 weeks), and after course 6 (24 weeks) of treatment with Ra-223. After completion of study, patients are followed up for up to 12 months.

Official Title
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Combined One Stop Shop NaF/FDG PET/MRI Evaluation of Response to Xofigo® in mCRPC Patients: A Pilot Study

Conditions
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Hormone-Resistant Prostate Cancer, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma

Intervention / Treatment
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* Procedure: Contrast-enhanced Magnetic Resonance Imaging
* Drug: Fludeoxyglucose F-18
* Drug: Fluorine F 18 Sodium Fluoride
* Procedure: Magnetic Resonance Imaging
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provides written informed consent Diagnosed with mCRPC and painful bone metastases, referred for Xofigo (radium Ra 223 dichloride) Able to remain still for duration of the imaging procedure (about one hour) Exclusion Criteria: Metallic implants

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (18F NaF/18F FDG PET/MRI, contrast-enhanced MRI)<br>Patients receive 18F NaF and 18F FDG IV over 30 seconds-1 minute and then undergo PET/MRI and contrast-enhanced MRI after 45-60 minutes. Patients undergo imaging at baseline, after course 3 (12 weeks), and after course 6 (24 weeks) of treatment with Ra-223. | Procedure: Contrast-enhanced Magnetic Resonance Imaging<br>* Undergo contrast-enhanced MRI<br>* Other names: Contrast-enhanced MRI;Drug: Fludeoxyglucose F-18<br>* Given IV<br>* Other names: Fluorodeoxyglucose F18;Drug: Fluorine F 18 Sodium Fluoride<br>* Given IV<br>* Other names: F-18 NaF;Procedure: Magnetic Resonance Imaging<br>* Undergo PET/MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Procedure: Positron Emission Tomography<br>* Undergo PET/MRI<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dichotomized treatment response at 24 weeks, based on technetium Tc-99m medronate (99mTc-MDP) bone scintigraphy intensity | Logistic regression of per-lesion 24-week response will be performed on percent reduction in lesion maximum standardized uptake value and percent reduction in lesion MR size. The logistic regression will include an adjustment for clustering. The receiver operating characteristic curve from the logistic regression will be graphed to give some idea of the relative sensitivity and specificity of the model. | 24 weeks | 
| Dichotomized treatment response at 24 weeks, based on computed tomography (CT) lesion size | Logistic regression of per-lesion 24-week response will be performed on percent reduction in lesion maximum standardized uptake value and percent reduction in lesion MR size. The logistic regression will include an adjustment for clustering. The receiver operating characteristic curve from the logistic regression will be graphed to give some idea of the relative sensitivity and specificity of the model. | 24 weeks | 
| Dichotomized treatment response at 24 weeks, based on alkaline phosphatase (ALP) measurements (per lesion analysis) | Logistic regression of per-lesion 24-week response will be performed on percent reduction in lesion maximum standardized uptake value and percent reduction in lesion MR size. The logistic regression will include an adjustment for clustering. The receiver operating characteristic curve from the logistic regression will be graphed to give some idea of the relative sensitivity and specificity of the model. | 24 weeks | 
| Percent reduction at 12 weeks in NaF/FDG PET standardized uptake value |  | 12 weeks | 
| Percent reduction at 12 weeks in MRI lesion size (per lesion analysis) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of new or regrowing extra-skeletal disease at 12 and/or 24 weeks on NaF/FDG PET/MRI that is not present on corresponding standard-of-care 99mTc-MDP bone scintigraphy and CT (per lesion analysis) |  | Up to 24 weeks | 
| True status (true positive or false positive) of such lesions after 12 months of follow-up, based on all information except NaF/FDG PET/MRI (per lesion analysis) | The true positive fraction of progressions detected only with NaF/FDG PET/MRI will be estimated with 95% confidence intervals. | 12 months |