[18]F-Fluciclatide for Kidney Cancer Imaging Studies and Treatment

BACKGROUND:

- Fluciclatide is a small cyclic peptide containing the RGD tri-peptide, which
preferentially binds with high affinity to Alpha(v)Beta(3) integrins, which are
up-regulated in and may regulate angiogenesis.

- Alpha(v)Beta(3) integrins are also expressed on certain types of tumor cells, such as
renal cell cancer.

- [18F] Fluciclatide (previously known as 18F-AH111585) is a new radiopharmaceutical
developed for PET imaging, which targets Alpha(v)Beta(3) receptors.

- Initial and ongoing clinical studies performed in Europe and an ongoing multicenter
phase 2 proof-of-concept study (which is currently open at the NIH Clinical Center);
demonstrate to date that [18F] Fluciclatide is safe and well tolerated.

PRIMARY OBJECTIVE:

- To determine tumor uptake and retention of [18F] Fluciclatide before and after 1 cycle of
treatment with targeted anti-angiogenic therapy in renal cell cancer.

ELIGIBILITY:

- Adult subjects (greater than or equal to18 years old), with documented renal or
metastatic renal cancer, with at least one tumor greater than or equal to1 cm in
diameter outside of the liver, who are scheduled to enroll in a therapy protocol using
an anti-angiogenic agent.

- The subject has a platelet count of > 100,000 times 10(6)/L, hemoglobin value of > 9
g/dL, prothrombin time (PT) and an activated partial thromboplastin time (aPTT) within
< 2 times normal limits.

- The subject has not received any targeted anti-angiogenic agents within 60 days prior
to pre-treatment (baseline) [18F] Fluciclatide PET imaging.

DESIGN:

This will be a pilot, open-label, proof-of-concept study to assess the magnitude of changes
in [18F] Fluciclatide PET tumor uptake following treatment with an anti-angiogenic therapy.
We expect to enroll 30 evaluable patients in this single center study. When possible, the
data analysis will be stratified based on the anti-angiogenic agent received. Subjects will
undergo at least two [18F] Fluciclatide PET/CT imaging studies, one pre-therapy and one
following completion of 1 cycle of therapy. An optional early post-therapy (2-7 days post
therapy commencement) [18F] Fluciclatide PET/CT may be performed. The magnitude of [18F]
Fluciclatide uptake on the preand post- treatment PET/CT studies will be evaluated to
determine if there is a measureable difference in uptake. Subjects may also undergo standard
of care imaging studies as part of routine tumor assessments specified in referring
protocols (e.g. diagnostic CT, FDG-PET/CT, etc). Data from the subject s referring therapy
protocol will be reviewed for up to one year after anti-angiogenic therapy initiation to
assess for tumor response or progression and its relationship to [18F] Fluciclatide PET/CT
imaging. Some patients will also undergo optional DCE-MRI scans of the target lesion and in
those subjects a comparison between MR parameters and [18F]

Fluciclatide parameters will be made.

- INCLUSION CRITERIA:

- Adult subjects (greater than or equal to18 years old), with documented renal
malignancy or metastatic renal cancer, with at least one tumor greater than or equal
to1 cm in diameter (not within the liver), who are scheduled for treatment using an
anti-angiogenic therapy agent

- Platelet count of > 100,000 times 10(6)/L, hemoglobin value of > 9 g/dL, PT and an
aPTT < 2 times normal limits.

- Clinically acceptable medical history, physical examination and vital signs findings
during the screening period (from < 4 weeks before administration of [18F]
Fluciclatide); i.e. Eastern Cooperative Oncology Group (ECOG) performance score of 0
to 2.

- The subject has had no open surgical wounds in close proximity to the target
lesion(s) within 10 days prior to study entry.

- The subject has not had a needle/core biopsy of the target lesion within 10 days of
PET/CT imaging.

- The subject has not had radiation therapy to the region of the target lesion.

EXCLUSION CRITERIA:

- The subject is pregnant or nursing.

- The subject is being treated with doses of heparin or warfarin resulting in elevation
of PT or aPTT > 2 times normal.

- The subject has received any anti-angiogenic agent (e.g. bevacizumab, sorafenib,
sunitinib) within 60 days prior to pre-treatment (baseline) [18F] Fluciclatide PE
imaging. This stipulation does not apply after the baseline [18F] Fluciclatide PET
imaging.

- The subject has any contraindication to any of the study procedures, products used or
its constituents (e.g. severe claustrophobia unrelieved by oral anxiolytics).

- The subject is unable to lie still for 75 minutes.

2.1.2.6 The subject is known to have a history of hyper- or hypo-coagulation syndromes
resulting in prolongation of bleeding parameters. Such coagulopathies include but are not
limited to Von Willebrand disease, Protein C deficiency, Protein S deficiency, Hemophilia
A/B/C, Factor-V Leiden, and Bernard-Soulier syndrome.

- The subject has undergone a surgical procedure to the target lesion within 28 days
prior to baseline [18F] Fluciclatide administration OR is scheduled to undergo a
surgical procedure between the baseline and post 1-cycle [18F] Fluciclatide PET/CT.

- The subject has only bone metastasis

ADDITIONAL EXCLUSION CRITERIA FOR SUBJECTS UNDERGOING OPTIONAL MR:

- Serum creatinine within 2 weeks prior to MRI greater than or equal to1.8mg/dl OR
estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m(2).

- The subject has known allergy to gadolinium

2.1.3.3 The subject has contraindications to MRI

- Subjects must weigh < 136 kg (weight limit for scanner table).

- Subjects cannot have pacemakers, cerebral aneurysm clips, shrapnel injury, or other
implanted electronic devices or metal not compatible with MRI.