A Phase II Study to Evaluate Axumin PET/CT for Risk Stratification for Prostate Cancer

Study Overview
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Brief Summary
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To investigate the utility of fluciclovine F 18 for evaluation for metastatic disease in men undergoing laser focal therapy of prostate cancer and the impact on inclusion for a focal therapy cohort.

Detailed Description
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DESCRIPTION OF DRUG Mechanism of action: Fluciclovine F 18 is a synthetic amino acid transported across mammalian cell membranes by amino acid transporters, such as LAT-1 and ASCT2, which are upregulated in prostate cancer cells. Fluciclovine F 18 is taken up to a greater extent in prostate cancer cells compared with surrounding normal tissues. Pharmacodynamics: Following intravenous administration, the tumor-to-normal tissue contrast is highest between 4 and 10 minutes after injection, with a 61% reduction in mean tumor uptake at 90 minutes after injection. Pharmacokinetics: Distribution: Following intravenous administration, fluciclovine F 18 distributes to the liver (14% of administered activity), pancreas (3%), lung (7%), red bone marrow (12%) and myocardium (4%). With increasing time, fluciclovine F 18 distributes to skeletal muscle. Excretion: Across the first four hours post-injection, 3% of administered radioactivity was excreted in the urine. Across the first 24 hours post-injection, 5% of administered radioactivity was excreted in the urine. TEST PRODUCT, DOSE, AND ROUTE OF ADMINISTRATION All subjects will receive a single IV dose of 10mCi (370MBq) +20%18F-fluciclovine immediately prior to PET scan. Administration: Prior to PET/CT, 10mCi ±20% of 18F-fluciclovine will be administered as an IV bolus injection followed by a 10 mL saline flush, with the subject lying in a supine position. The dose will be injected into an antecubital vein or another vein that will provide access. The administration site will be evaluated pre- and post- administration for any reaction (e.g. bleeding, hematoma, redness, or infection). Documentation of administration to a subject will be recorded according to standard of care, including start of administration, injection site, date, prescription number, total volume and total radioactivity. Packaging, Labeling and ordering: Fluciclovine F 18 is supplied as a unit dose for injection in a syringe with a radioactive concentration at a reference date and time that is stated on the container label. Each syringe is supplied in a container providing appropriate radiation shielding. Information will be provided with the shipment giving the confirmation number, radioactive concentration of injection (mCi/mL) at a stated time and date, shelf life information, protocol number and a unique prescription number. The radiochemical purity of 18F-fluciclovine injection is not less than 95% during the shelf life of the product. The order for a specific patient at a specific date and time must be made to PETNET Solutions Centralized Scheduling Team (Tel: 1 877 473 8638) and will be delivered from the radiopharmacy to the imaging site by courier. Indian Wells PET/CT Center will keep records of all shipments of fluciclovine F 18 received, dispensing and disposal/destruction performed on site in accordance with ACR and NCRP guidelines. Imaging protocol. The recommended dose is 370 MBq (10 mCi) administered as an intravenous bolus injection. Begin PET scanning 3 to 5 minutes after completion of the Axumin injection Proximal thigh to skull base x 5min/bed position caudocranial direction Recon: Iterative Iterations - 2, Subsets - 8 Filter Gaussian Image interpretation: Image interpretation will be based on guidelines outlined in and derived from an international 18F-fluciclovine Reader Consensus Meeting held in June 2014 (see References) and will follow processes similar to those outlined on the on-line Axumin™ (fluciclovine F 18) Image Interpretation Training (http://jnm.snmjournals.org/content/58/10/1596.long) . Reader has undergone training in interpretation of 18F- fluciclovine PET/CT scans, and has a training set available for reference. 1. Non-Significant Risk Study Desert Positron Imaging has identified this investigation as a Non-Significant Risk (NSR) study. PRELIMINARY WORK 1. CLINICAL STUDIES: The safety and efficacy of Axumin were evaluated in two studies (Study 1 and Study 2) in men with suspected recurrence of prostate cancer based on rising PSA levels following radical prostatectomy and/or radiotherapy. Study 1 evaluated 105 Axumin scans in comparison to histopathology obtained by biopsy of the prostate bed and biopsies of lesions suspicious by imaging. PET/CT imaging generally included the abdomen and pelvic regions. The Axumin images were originally read by on-site readers. The images were subsequently read by three blinded independent readers. Table 4 of the package insert for Axumin shows the performance of Axumin in the detection of recurrence in each patient scan and, specifically, within the prostate bed and extra-prostatic regions, respectively. The results of the independent read were generally consistent with one another and confirmed the results of the on-site reads. In general, patients with negative scans had lower PSA values than those with positive scans. The detection rate (number with positive scans/total scanned) for patients with a PSA value of less than or equal to 1.78 ng/mL (1st PSA quartile) was 15/25, of which 11 were histologically confirmed as positive. In the remaining three PSA quartiles, the detection rate was 71/74, of which 58 were histologically confirmed. Among the 25 patients in the first PSA quartile, there were 4 false positive scans and 1 false negative scan. For the 74 patients with PSA levels greater than 1.78 ng/mL, there were 13 false positive scans and no false negative scans. Study 2 evaluated the concordance between 96 Axumin and C11 choline scans in patients with median PSA value of 1.44 ng/mL (interquartile range = 0.78 to 2.8 ng/mL). The C11 choline scans were read by on-site readers. The Axumin scans were read by the same three blinded independent readers used for Study 1. The agreement values between the Axumin and C11 choline reads were 61%, 67% and 77%, respectively.

Official Title
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A Phase II Study to Evaluate Axumin PET/CT for Risk Stratification for Laser Focal Therapy of Intermediate Risk Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Axumin PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, 45 years of age or older. Diagnosis of prostate adenocarcinoma. Clinical stage T1a, T1b, T1c, T2a, T2b orT2c. Gleason score of 7 (3+4 or 4+3). PSA density less than 0.375. One, two, or three tumor suspicious regions identified on multiparametric MRI. Negative radiographic indication of extra-capsular extent. Karnofsky performance status of at least 70. Estimated survival of 5 years or greater, as determined by treating physician. Tolerance for anesthesia/sedation. Ability to give informed consent. Exclusion Criteria: Presence of any condition (e.g., metal implant, shrapnel) not compatible with MRI. Severe lower urinary tract symptoms as measured by an International Prostate Symptom Score (IPSS) of 20 or greater. ( (http://www.urospec.com/uro/Forms/ipss.pdf) History of other Primary non-skin malignancy within previous three years. Diabetes. Smoker.

Ages Eligible for Study
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Minimum Age: 45 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
Interventional Model Description: Cohort
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Men with Gleason Score 7 prostate cancer<br>Men seeking focal therapy for Gleason Score 7 prostate cancer will receive Axumin PET/CT imaging to detect metastasis which will result in exclusion from laser focal therapy. | Drug: Axumin PET/CT<br>* Synthetic amino acid uptake agent injection followed by imaging<br>* Other names: PET/CT scan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of Metastases | Number of patients with detection of metastasis Secondary Outcome Measure Description: Number of patients with local uptake of Axumin | One day |