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.

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 Axuminâ„¢ (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.