Imaging Biomarkers to Validate Response in Enzalutamide-Treated mCRPC

Study Overview
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Brief Summary
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To determine the feasibility and success rate of tumor tissue procurement using molecular-image-directed biopsies of responding and non-responding osseous metastases, measured by NaF PET/CT, in patients with metastatic castrate-resistant prostate cancer.

Official Title
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Validation of Imaging-Based Biomarkers of Treatment Response in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Other: 18F-Sodium Fluoride (NaF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven adenocarcinoma of the prostate. Identifiable prostate cancer-related osseous metastases on bone scan or NaF PET/CT in the vertebral body, pelvis or other bone. Such lesions must be amenable to serial NaF PET/CT imaging. Preference will be given to subjects with multiple lesions that can be imaged in one image acquisition session to obtain maximal information as well as locations of lesions amenable to bone biopsies. Patients must be starting enzalutamide for treatment of metastatic castrate-resistant prostate, with cycle 1 day 1 occurring within 14 days after the first baseline NaF PET/CT. Subjects will be allowed to receive enzalutamide treatment on a concurrent study as long as the enzalutamide treatment study does not prohibit concurrent participation. Men of all races and ethnic groups of age ≥18 years. The effects of NaF on the developing human fetus are unknown. For this reason and because radiopharmaceuticals used for diagnostic imaging and other therapeutic agents and imaging procedures used in this trial may be or are known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately. Patients must be able to comply with all study procedures, including having both the ability and willingness to lie flat for ≥ 30 minutes during imaging and undergo bone biopsies. Patients must have both the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Known bleeding diathesis or on therapeutic anticoagulants (warfarin, low-molecular heparin, heparin analogues) that would increase risk of complications from bone biopsies. History of allergic reactions attributed to compounds of similar chemical or biologic composition to sodium fluoride F-18 (NaF).

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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: 18F-Sodium Fluoride (NaF)|NaF is a tracer (dye) that will show changes to the cancer in bones. By using this tracer with PET/CT imaging, our ability to evaluate and measure changes in bone lesions could be greatly improved. Participants will have a NaF PET/CT scan within 14 days prior to starting enzalutamide. All subjects will undergo a second NaF PET/CT scan after taking enzalutamide for 12 weeks. The NaF PET/CT obtained at week 12 will be compared to the first NaF PET/CT to identify a bone tumor that is responding (shrinking) and a bone tumor that is not responding (not shrinking).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of biopsies obtained from NaF PET/CT- identified responding and non-responding bone metastases that contain tumor tissue from 30 patients | To determine the feasibility and success rate of tumor tissue procurement using molecular-image-directed biopsies of responding and non-responding osseous metastases, measured by NaF PET/CT, in patients with metastatic castrate-resistant prostate cancer. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of known response molecular biomarkers obtained from responding lesions as identified using NaF PET/CT in 30 patients who have received 12 weeks of enzalutamide. | To compare NaF PET/CT responding lesions to known response molecular biomarkers obtained from biopsy of responding lesions | Within 2 weeks of week 12 | 
| The number of patients whose biopsy tissue demonstrates at least 5 markers from a panel of 300 individual markers that have a moderate effect size of 1.0 or greater for the difference between the enzalutamide resistant and responding bone metastases | To compare NaF PET/CT non-responding lesions to known resistance molecular biomarkers obtained from biopsy of non-responding lesions | Within 2 weeks of week 12 | 
| Characterizations obtained from NaF PET/CT images from patients who demonstrate a progression free survival of greater than 12 months on enzalutamide treatment. | To determine NaF PET/CT -derived radiomic profiles that correlate with prolonged benefit (PFS > 12 month) to enzalutamide | Within 2 weeks of week 12 | 
| Comparison of the percentage of responding/non-responding lesions on NaF PET/CT to PSA response, RECIST response, time to PSA progressions and radiographic progression free survival | To correlate global responsiveness on NaF PET/CT (percentage of responding/non-responding lesions, SUVtotal) with clinical outcomes: PSA response, RECIST response, time to PSA progressions, and radiographic PFS | Within 2 weeks of week 12 |