Gadoxetate Enhanced Imaging Study to Detect Prostate Cancer

BACKGROUND:

- Prostate cancer is the most common non-cutaneous malignancy among men in the western
world. Prognostic biomarkers would be useful in stratifying patients to different
treatments.

- The expression of a testosterone membrane transporter, organic anion-transporting
polypeptide 1B3 (OATP1B3), is associated with shorter time to progression after hormonal
ablation therapy and shorter overall survival in prostate cancer patients. 52% of
localized prostate cancer lesions express OATP1B3, while 92% of prostate cancer
metastases requiring hormonal ablation treatment, express OATP1B3 in soft tissue
lesions. Expression of OATP1B3 also correlates with Gleason grade.

- Current imaging methods cannot predict treatment failure or resistance.

- Gadoxetate disodium (Gd-EOB-DTPA) (Eovist , Bayer HealthCare Pharmaceuticals Inc.
Pittsburgh, PA) is an MR imaging agent which is FDA-approved gadolinium chelate for
detecting hepatocellular carcinoma (HCC), as normal hepatocytes express OATP1B3 while
most hepatocellular carcinomas (HCC) do not. However, those HCCs that do take up Eovist
have been shown to express OATP1B3.

- Eovist may be useful to evaluate OATP1B3 status in patients with prostate cancer and may
therefore serve as a prognostic and treatment biomarker.

PRIMARY OBJECTIVE:

-Evaluate the uptake and retention of Eovist in prostate cancers.

ELIGIBILTY:

- Male subjects greater than or equal to 18 years old

- Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2

- Subjects with clinically localized prostate cancer must have image guided biopsy
confirmed prostate cancer and sufficient tissue available for OATP1B3
immunohistochemistry (IHC).

- Subjects with advanced disease who have failed hormone therapy and who have sufficient
tissue from a soft tissue or metastatic bone lesion (measuring greater than or equal
to1.5cm in diameter at computed tomography (CT) or magnetic resonance imaging (MRI)
scan) available for OATP1B3 IHC.

or

-Subjects, for whom tissue is not available, must have a soft tissue or metastatic bone
lesion that can be biopsied and be willing to undergo percutaneous biopsy to obtain tissue
for OATP1B3 expression.

DESIGN:

- This pilot study will accrue 25 subjects divided into two arms: 10 evaluable subjects
with localized prostate cancer and 15 evaluable subjects with advanced disease

- Each subject will receive a single intravenous (IV) dose of Eovist by bolus injection

- All subjects will undergo magnetic resonance imaging (MRI) prior to and immediately
after, 10, 20 and 60 minutes post-Eovist injection

- INCLUSION CRITERIA:

2.1.1.1 Subject is greater than or equal to 18 years old.

2.1.1.2 Subjects with clinically localized prostate cancer (outside pathology is
acceptable) must have image guided biopsy confirmed prostate cancer and sufficient tissue
available (obtained before or after 20 weeks of Eovist injection) for organic
anion-transporting polypeptide 1B3 (OATP1B3) expression.

2.1.1.3 Subjects with advanced disease who have failed hormone therapy and who have
sufficient tissue (obtained before or after 20 weeks of Eovist injection) from a soft
tissue lesion (measuring greater than or equal to 1.5cm in diameter at computed tomography
(CT) or magnetic resonance imaging (MRI) scan) available for OATP1B3 expression.

or

2.1.1.4 Subjects, for whom tissue is not available, must have a soft tissue or metastatic
bone lesion that can be biopsied and be willing to undergo percutaneous biopsy to obtain
tissue for OATP1B3 expression.

2.1.1.5 Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
2

2.1.1.6 Serum creatinine within 3 weeks prior to Eovist MRI less than or equal to 1.8mg/dl
and estimated glomerular filtration rate (eGFR) must be greater than 30 ml/min/1.73m(2).

2.1.1.7 Patients must have normal liver function as defined below:

- total bilirubin less than 2 times normal institutional limits or greater than 3.0
mg/dl in patients with Gilberts syndrome

- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and
alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or
equal to 3 times institutional upper limit of normal

2.1.1.8 Ability of subject to sign a written informed consent document

EXCLUSION CRITERIA:

2.1.2.1 Subjects with known hypersensitivity and allergy to gadolinium contrast agents

2.1.2.2 Subjects with any coexisting medical or psychiatric condition that is likely to
interfere with study procedures and/or results

2.1.2.3 Subjects with severe claustrophobia unresponsive to oral anxiolytics

2.1.2.4 Subjects with contraindications to magnetic resonance imaging (MRI)

2.1.2.5 Subjects weighing greater than 136 kg (weight limit for scanner table)

2.1.2.6 Subjects with pacemakers, cerebral aneurysm clips, shrapnel injury, or other
implanted electronic devices or metal not compatible with MRI

2.1.2.7 Subjects with other medical conditions deemed by the principle investigator (or
associates) to make the subject ineligible for protocol procedures

2.1.2.8 Subjects who will have a delay in clinically indicated radiation therapy due to the
interval between Eovist MRI imaging and biopsy