Sunitinib for Metastatic Renal Cell Cancer With Imaging Biomarker Assessments for the Early Prediction of Tumor Response
Condition: Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell
Intervention: Sunitinib
Intervention description: Imaging studies with complete analyses will be provided on all patients prior to institution of sunitinib therapy as well as after therapy at various early time points (1 week in 5 patients, 2 weeks in 5 patients, 3 weeks in 5 patients or 4 weeks in 5 patients) after institution of sunitinib therapy at 37.5 mg orally/day.
Imaging studies include:
FDG-PET scans FLT-PET scans H215O-PET scans DCE-MRI scans
Intervention MeSH terms: Sunitinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This exploratory clinical study is designed to obtain pre-therapeutic imaging assessments in
      20 evaluable patients with metastatic renal cell cancer (RCC) and an early post therapy
      assessment at baseline and at various early time points (1 week in 5 patients, 2 weeks in 5
      patients, 3 weeks in 5 patients and 4 weeks in 5 patients) after institution of standard
      approved sunitinib therapy at 37.5 mg/day. The clinical imaging biomarkers will include an
      assessment of tumor metabolism [Bannasch 1986, Frauwirth 2002, Garber 2006, Kelloff 2005,
      Pauwels 1998, Semenza 2001, Smith 1999, Smith 2000, Sokoloff 1977, Warburg 1956, Weber 1977A,
      Weber 1977B] (dynamic FDG-PET); tumor proliferation [Rasey 2002,Shields 2001, Shields 1998,
      Vesselle 2002, Schwartz 2003] (dynamic FLT-PET); tumor blood flow (H215O-PET, DCE MRI)[Lodge
      2000], tumor perfusion (DCE-MRI)[Tofts 1999, Tofts 1997, Parker 1999]; and tumor blood volume
      (H215O-PET, DCE MRI)[Lodge 2000, Tofts 1999, Tofts 1997] 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). We hypothesize that by using this set of imaging assessments it will be possible to
      determine an individual or more likely a set of imaging derived biomarkers that will
      accomplish several of the goals of the initiative which is providing funding for the study.
    

Eligibility criteria:

        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.