Sunitinib for Metastatic Renal Cell Cancer With Imaging Biomarker Assessments for the Early Prediction of Tumor Response

Our proposed clinical study will:

- Provide an exploratory yet reliable and validated cadre of imaging studies done in
patients that yield a mechanistically-based understanding of: 1) predictive assays for
clinical benefit from standard sunitinib therapy, 2) measurement of efficacy during
standard sunitinib therapy, and 3) prognosis or other long term outcomes.

- Reveal a more detailed understanding of the in vivo mechanism of standard sunitinib
therapy in patient tumors, mechanistic information on why particular functional imaging
patterns are seen in treated patients, and clinical measures that are useful to
physicians for decision making and for explanation of efficacy or outcomes for
patients.

- Predict which patients may benefit from standard sunitinib therapy.

- Determine early in the course of treatment whether standard sunitinib therapy will be
efficacious and whether this can be used in future comparable patients.

- Show the outcome of patients with standard sunitinib treatment.

- Shed further information on the biological mechanism for the rapid decrease of FDG
uptake on FDG-PET imaging with standard sunitinib treatment.

It is our hypothesis that a set of biologically relevant imaging biomarkers (tumor
metabolism assessed with dynamic FDG-PET; tumor proliferation assessed with dynamic FLT-PET;
tumor blood flow assessed with H215O-PET and DCE MRI); tumor perfusion assessed with
DCE-MRI; and tumor blood volume/volume of distribution assessed with H215O-PET and DCE MRI)
in the same patient at baseline and then in the same patient at one of the post therapy time
points (1 week, 2 weeks, 3 weeks or 4 weeks) will provide either alone or more likely in
combination information that will predict which patients will most likely benefit from
standard sunitinib therapy and that an early response assessment is possible that is
predictive of a durable response to the therapeutic drug.

Inclusion Criteria:

- Patients must be 18 years or older for inclusion in this study. Since there is no
experience with [F-18]FLT in children and it would be inappropriate to study
individuals under the age of 18 until more safety data is available.

- After entry into the study, patients are expected to be followed for at least 2
months as part of standard of care.

- All patients, or their legal guardians, must sign a written informed consent and
HIPAA authorization in accordance with institutional guidelines.

- The patient, if female, must be postmenopausal for a minimum of one year or
surgically sterile, or on one of the following methods of birth control for a
minimum of one month prior to entry into this study: IUD, oral contraceptives,
Depo-Provera or Norplant. These criteria can be waived at the discretion of the
investigator if the patient's tumor is considered life threatening and the one
month wait required is not in the best interest of the patient. Negative
pregnancy test is accepted.

- Pre-treatment laboratory tests for patients receiving [F-18]FLT must be
performed within 21 days prior to study entry. These must be less than 4 times
below or above the upper or lower limit range for the respective laboratory
test. These will include liver enzymes (SGOT, SGPT, ALK Phos, GGT, LDH),
bilirubin (direct and total), amylase, serum electrolytes, CBC with platelets
and absolute neutrophil counts, prothrombin time, partial thromboplastin time,
BUN, creatinine, and urinalysis.

- Pre-treatment radiological clinical scans/studies (Gd- enhanced MRI or CT
to document metastatic renal cell carcinoma) must be performed within 30
days of study entry.

Exclusion Criteria:

- Patients with known allergic or hypersensitivity reactions to previously administered
radiopharmaceuticals or Gd used in MRI imaging. Patients with significant drug or
other allergies or autoimmune diseases may be enrolled at the Investigator's
discretion.

- Patients who are pregnant or lactating or who suspect they might be pregnant.

- Adult patients who require monitored anesthesia for PET or MRI scanning.

- HIV positive patients due to the previous toxicity noted with FLT.

- Renal Insufficiency Exclusion for MRI contrast injection. All subjects will be
screened as to their renal status and those patients with renal insufficiency
will be excluded from undergoing a dynamic contrast enhanced MRI scan. This is
in response to the recent association of MRI contrast agents with the
development of Nephrogenic Systemic Fibrosis (NSF). The patient will have a
creatinine value determined within 4 weeks prior to the proposed MRI scan and
have a GFR determined from the creatinine value and other data that can be used
at various websites to determine the GFR. If the GFR is greater than 60
ml/min/then the patient will be deemed eligible for contrast injection. If the
GFR value is between 40 ml/min and 60 ml/min the risk versus benefit of
performing the contrast injection will be discussed with the referring physician
and the patient. If the GFR is less than 40 ml/min the dynamic contrast study
will not be performed. The non-contrast MRI scan however will be obtained for
anatomic reference for the PET studies.

MRI exclusion criteria:

- Presence of any ferromagnetic metallic implants or foreign bodies, including
pacemakers and certain types of stents and orthopedic hardware.

- Claustrophobia or inability to remain stationary within MRI system for ~30-45
minutes.

- Inability to breath hold for periods of at least 20 seconds.

- Known history of adverse reaction to Gd chelate contrast agents.

- Pregnancy or breastfeeding.

- Non-imageable tumor, including tumors with smallest dimension less than 10mm or
tumors located in regions excessively affected by susceptibility artifacts at bone-
and air-tissue interfaces or motion artifacts due to peristalsis or pulsatile flow.