Carbon-11 Acetate and Fluorine F 18 Sodium Fluoride PET as a Biomarker of Treatment Response in Patients With Hormone Resistant Metastatic Prostate Cancer

Study Overview
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Brief Summary
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This clinical trial studies carbon-11 acetate and fluorine F 18 sodium fluoride positron emission tomography (PET) as a biomarker of treatment response in patients with prostate cancer that does not respond to treatment with hormones and has spread to other parts of the body. Carbon-11 acetate and fluorine F 18 sodium fluoride are radioactive drugs that may be useful in evaluating prostate cancer activity in response to treatment. Comparing results of diagnostic procedures such as carbon-11 acetate and fluorine F 18 sodium fluoride PET done before and after therapy may help doctors predict a patient's response to treatment and help plan the best treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. Demonstrate that carbon-11 acetate (11C-acetate) and 18F-fluoride (fluorine F 18 sodium fluoride) PET scans change as a result of treatment for men with metastatic castration-resistant prostate cancer by comparison of pre-treatment and 6-12 week post-treatment images (standardized uptake value [SUV], influx constant [Ki], and rate constant [K1]) with clinical response measures. SECONDARY OBJECTIVES: I. Compare results from 11C-acetate and 18F-fluoride PET scanning with the patient's clinical bone scan and determine which predicts clinical response better. II. Compare changes in 11C-acetate and 18F-fluoride PET with changes in prostate-specific antigen (PSA) level. III. Compare changes in 11C-acetate and 18F-fluoride PET with changes in urinary N-telopeptide and bone alkaline phosphatase. IV. Determine if either baseline uptake or change in uptake for 11C-acetate and/or 18F-fluoride PET is correlated with progression-free survival by Prostate Cancer Working Group 2 (PCWG2) criteria (Scher, 2008). V. Determine if either baseline uptake or change in uptake by 11C-acetate and/or 18F-fluoride PET is correlated with skeletal-related events (SREs) defined as radiographic pathologic fracture, need for radiation to bone, need for surgery, spinal cord compression or malignant hypercalcemia. VI. Percentage of patients that experience adverse events by Common Terminology Criteria for Adverse Events, version 4.0. VII. For patients who have tissue/blood biomarkers obtained for other indications, directly compare baseline uptake and change in uptake by 11C-acetate and/or 18F-fluoride PET with those biomarkers. OUTLINE: Patients receive carbon-11 acetate intravenously (IV) and fluorine F 18 sodium fluoride IV over 1 minute and undergo PET at baseline and at 6-12 weeks after systemic therapy starts. After completion of treatment, patients are followed up every 3 months for up to 5 years.

Official Title
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PET Imaging as a Biomarker of Systemic Treatment Response for Men With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

Intervention / Treatment
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* Radiation: carbon-11 acetate
* Radiation: fluorine F 18 sodium fluoride
* Procedure: positron emission tomography
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients preparing to receive systemic therapy to treat metastatic castration-resistant prostate cancer At the time of enrollment, patients must demonstrate evidence of castration-resistant prostate cancer with a documented castrate level of serum total testosterone (< 50 ng/dL) while on continuous androgen deprivation therapy Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific screening procedures Be willing and able to comply with scheduled visits and other trial procedures Presence of at least one measurable or detectable metastasis as defined by bone scintigraphy, computed tomography (CT) scan appearance (magnetic resonance imaging [MRI] if indicated), or plain x-ray appearance Exclusion Criteria: Any condition that would alter the patient's mental status, prohibiting the basic understanding and/or authorization of informed consent A serious underlying medical condition that would otherwise impair the patient's ability to receive treatment and imaging studies Expected lifespan of 12 weeks or less Extremely poor intravenous access, prohibiting the placement of a peripheral IV line for injection of radiotracer Radiation treatment to bone less than 4 weeks from the first PET scan Radiopharmaceutical treatment to bone less than 4 weeks from first PET scan Treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte (G-CSF) within 4 weeks prior to first PET scan; patients should avoid treatment with these agents between the baseline and 6-12 treatment week imaging sessions Inability to lie still for imaging Weight > 300 pounds (lbs)

Ages Eligible for Study
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Minimum Age: 18 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 (11C-acetate, 18F-fluoride, PET)<br>Patients receive carbon-11 acetate IV and fluorine F 18 sodium fluoride IV over 1 minute and undergo PET at baseline and at 6-12 weeks after systemic therapy starts. | Radiation: carbon-11 acetate<br>* Given IV<br>Radiation: fluorine F 18 sodium fluoride<br>* Given IV<br>* Other names: F-18 NaF;Procedure: positron emission tomography<br>* Undergo 11C-acetate and 18F-fluoride PET<br>* Other names: tomography, emission computed;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in prostate cancer metastases as measured by 11C-acetate and 18F-fluoride PET in response to systemic therapy | Percentage change between pre-treatment and post-therapy measurements will be computed for PET measures. Log transformations will be considered if the rates of change are highly skewed. Additionally, changes in PET measures will be analyzed descriptively by a stem-and-leaf plot. | Baseline to up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response data (response, stable disease or progression) | Molecular imaging measures and clinical measures of treatment response, percentage change in PET derived imaging data will be compared to standard clinical parameters. Association between these two types of data decline will be analyzed using the mid-P adjustment to Fisher's exact test (Lancaster, 1961) to evaluate the potential clinical utility of change in 11C-acetate and 18F-fluoride as a biomarker for response. | Up to 5 years | 
| Proportion of both 11C-acetate and 18F-fluoride PET scans and 99mTc bone scans in discovering suspicious sites that are later confirmed by standard bone scans | Statistical significance of two proportions will be tested with a two-sample t-test for proportions (or nonparametric alternative). | Up to 5 years | 
| Change in PSA parameters | Spearman rank correlation will be used to examine correlations between PET parameters and continuous variable changes in PSA. | Baseline to up to 30 days post-PET | 
| Change in urinary N-telopeptide | Spearman rank correlation will be used to examine correlations between PET parameters and continuous variable changes in urinary N-telopeptide. | Baseline to up to 30 days post-PET | 
| Change in bone alkaline phosphatase | Spearman rank correlation will be used to examine correlations between PET parameters and continuous variable changes in bone alkaline phosphatase. | Baseline to up to 30 days post-PET | 
| Progression-free survival (PFS) using PCWG2 | Cox proportional hazards model will be used to investigate the predictive value of the differences in pre- and post- treatment measures on PCWG2 PFS. | Up to 5 years | 
| SRE defined as radiographic pathologic fracture, need for radiation to bone, need for surgery, spinal cord compression or malignant hypercalcemia | Cox proportional hazards model will be used to investigate the predictive value of the differences in pre- and post- treatment measures on time of first SRE. | Up to 5 years |