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.

Inclusion Criteria:

1. Male, 45 years of age or older.

2. Diagnosis of prostate adenocarcinoma.

3. Clinical stage T1a, T1b, T1c, T2a, T2b orT2c.

4. Gleason score of 7 (3+4 or 4+3).

5. PSA density less than 0.375.

6. One, two, or three tumor suspicious regions identified on multiparametric MRI.

7. Negative radiographic indication of extra-capsular extent.

8. Karnofsky performance status of at least 70.

9. Estimated survival of 5 years or greater, as determined by treating physician.

10. Tolerance for anesthesia/sedation.

11. Ability to give informed consent.

Exclusion Criteria:

1. Presence of any condition (e.g., metal implant, shrapnel) not compatible with MRI.

2. 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)

3. History of other Primary non-skin malignancy within previous three years.

4. Diabetes.

5. Smoker.