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

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.

1. The recommended dose is 370 MBq (10 mCi) administered as an intravenous bolus injection.
2. Begin PET scanning 3 to 5 minutes after completion of the Axumin injection
3. Proximal thigh to skull base x 5min/bed position caudocranial direction
4. Recon: Iterative
5. Iterations - 2, Subsets - 8
6. 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.