Fluorine F 18 Sodium Fluoride Positron Emission Tomography in Evaluating Response to Dasatinib in Patients With Prostate Cancer and Bone Metastases

Study Overview
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Brief Summary
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This phase II trial is studying how well fluorine F 18 sodium fluoride positron emission tomography (PET) works in evaluating response to dasatinib in patients with prostate cancer and bone metastases. Diagnostic procedures, such as fluorine F 18 sodium fluoride PET, 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. Determine if changes in regional fluoride incorporation, measured by 18F-fluoride PET (SUV and Ki), occur in both castration-resistant prostate cancer bone metastases and normal bone as a response to treatment with dasatinib. SECONDARY OBJECTIVES: I. Determine if changes in 18F-fluoride transport (K1), an indicator of blood flow, and therefore, an indirect marker of angiogenesis, occur in both castration-resistant prostate cancer bone metastases and normal bone as a response to treatment with dasatinib. OUTLINE: This is a multicenter study. Patients undergo fluorine F 18 sodium fluoride PET scan at baseline and then at 12 weeks after initiation of treatment with dasatinib. PET parameters (SUV, Ki, and Kl) are also analyzed.

Official Title
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A Phase 2, Multicenter Evaluation of 18F-Fluoride PET as a Pharmacodynamic Biomarker for Dasatinib, a Src Kinase Inhibitor, in Men With Castration-Resistant Prostate Cancer and Bone Metastases (BMS #180-279)

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

Intervention / Treatment
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* Radiation: Fluorine F 18 Sodium Fluoride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to provide a written informed consent Men 18 years or older with metastatic castration-resistant prostate cancer enrolling onto the Febbo clinical trial with dasatinib therapy (must meet all inclusion criteria for dasatinib treatment study and comply with requirements of that specific clinical trial) Histologic confirmation of original prostate cancer diagnosis Presence of at least one convincing bone metastasis as defined by bone scintigraphy, computed tomography (CT) scan (magnetic resonance imaging [MRI] if indicated), or plain X-ray Must currently have castrate testosterone levels (< 50 ng/dL) from orchiectomy or maintenance on a luteinizing hormone-releasing hormone (LHRH) agonist or LHRH antagonist Exclusion Criteria: On the nilutamide-only arm (Arm A of the clinical therapeutic trial) Note: However, if a patient crosses-over from nilutamide at the time of progression to add dasatinib therapy, he may be eligible for 18F-fluoride PET imaging protocol if he meets all inclusion criteria for this trial 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 Initiation of bisphosphonate therapy less than 4 weeks from the first PET scan Radiation treatment to bone less than 4 weeks from 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 CSF (G-CSF) within 4 weeks prior to first PET scan Inability to lie still for the imaging Weight > 300 lbs. (due to equipment specifications)

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: 18F-Fluoride PET<br>Patients undergo fluorine F 18 sodium fluoride PET scan at baseline and then at 12 weeks after initiation of treatment with dasatinib. Dasatinib was administered under a concurrent protocol and was not considered part of the intervention on this protocol | Radiation: Fluorine F 18 Sodium Fluoride<br>* Undergo fluorine F 18 sodium fluoride PET scan<br>* Other names: F-18 NaF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in 18F-fluoride PET (SUV) - Tumor Bone | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET in tumor bone as measured by SUVmax | Baseline and 12 weeks | 
| Changes in 18F-fluoride PET SUV - Normal Bone | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (SUV) in normal bone as measured by SUVmax | Baseline and 12 weeks | 
| Changes in 18F-fluoride Ki - Tumor Bone | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (Ki) in tumor bone. Ki represents the net uptake of fluoride to the bone mineral compartment and reflects the level of osteoblastic activity in bone | Baseline and 12 weeks | 
| Changes in 18F-fluoride Ki - Normal Bone | Investigation of changes between baseline and 12 weeks in regional fluoride incorporation as measured by 18F-fluoride PET (Ki) in normal bone. Ki represents the net uptake of fluoride to the bone mineral compartment and reflects the level of osteoblastic activity in bone | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in 18F-fluoride Transport (by Patlak Flux) - Tumor | Investigation of changes in regional fluoride incorporation as measured by 18F-fluoride transport (Patlak flux) in Tumor. This measurement uses the Patlak method for determining the influx constant. | Baseline and 12 weeks | 
| Changes in 18F-fluoride Transport (by Patlak Flux) - Normal | Investigation of changes in regional fluoride incorporation as measured by 18F-fluoride transport (Patlak flux) in normal bone. Palak flux is an indicator of blood flow and an indirect marker of angiogenesis. | Baseline and 12 weeks |