• Standard uptake value as measured by 3'-deoxy-3'-[18F] fluorothymidine (FLT)-PET/CT scans [ Designated as safety issue: No ]
  
• Objective response [ Designated as safety issue: No ]
  

• Plasma VEGF and HIF1-α levels [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Pharmacokinetic parameters [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the pharmacodynamic change using functional imaging (3'-deoxy-3'-[18F] fluorothymidine [FLT]-PET/CT scans) in patients with unresectable or metastatic clear cell renal cell carcinoma or other advanced solid malignancies treated with two different schedules of sunitinib malate.
• Evaluate the objective response in patients treated with this drug.

Secondary

• Measure the change in plasma VEGF levels and plasma HIF1-α levels as a potential mechanism for VEGFR tyrosine kinase inhibitor (TKI) failure and rapid tumor growth following VEGFR TKI withdrawal in these patients.
• Correlate pharmacokinetics of this drug with response, unexpected toxicity, VEGF levels, HIF1-α levels, and FLT-PET/CT scan changes.

OUTLINE: This is an open-label, nonrandomized study. Patients are stratified according to diagnosis (renal cell carcinoma vs other solid malignancy). Patients are assigned to 1 of 2 different treatment schedules of sunitinib malate.

• Schedule A: Patients receive oral sunitinib malate once daily in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
• Schedule B: Patients receive oral sunitinib malate once daily in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Blood is collected for pharmacokinetic studies periodically during course 1 and on day 1 of each subsequent course. Samples are analyzed for VEGF and HIF1-α by enzyme-linked immunosorbent assay. Patients also undergo functional imaging by 3'-deoxy-3'-[18F] fluorothymidine (FLT)-PET/CT scans to measure tumor proliferation in correlation with plasma VEGF levels and HIF1-α levels.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

  • Clear cell renal cell carcinoma
  • Other solid malignancy
• Metastatic or unresectable disease
• No standard curative therapy exists for disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• No lymphoma
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 12 weeks
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Calcium ≤ 12.0 mg/dL
• Total bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine ≤ 2 times ULN OR creatinine clearance ≥ 40 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate
• QTc interval ≤ 500 msec
• No significant cardiac abnormalities by ECG
• No poorly controlled hypertension (i.e., systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
• No condition that impairs the ability to swallow and retain sunitinib malate tablets (e.g., gastrointestinal [GI] tract disease resulting in an inability to take oral medication or a requirement for IV alimentation; prior surgical procedures affecting absorption; or active peptic ulcer disease)

• None of the following conditions are allowed:

  • Serious or nonhealing wound, ulcer, or bone fracture
  • Abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days
  • Cerebrovascular accident or transient ischemic attack within the past 12 months
  • Myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months
  • Pulmonary embolism within the past 12 months
  • NYHA class III-IV heart failure

• No preexisting thyroid abnormality with an inability to maintain normal thyroid function with medication

  • History of hyperthyroidism allowed provided patient is currently euthyroid
• No other uncontrolled illness, including, but not limited to, ongoing or active infections or psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 4 weeks since prior radiotherapy, experimental therapy, or major surgery
• No prior anti-VEGF agents

• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

  • Azole antifungals (ketoconazole, itraconazole)
  • Verapamil
  • Clarithromycin
  • HIV protease inhibitors (indinavir sulfate, saquinavir, ritonavir, atazanavir, nelfinavir mesylate)
  • Erythromycin
  • Delavirdine
  • Diltiazem hydrochloride

• At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following:

  • Rifampin
  • Phenytoin
  • Rifabutin
  • Hypericum perforatum (St. John's wort)
  • Carbamazepine
  • Efavirenz
  • Phenobarbital
  • Tipranavir
• No other concurrent investigational agents

• No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as warfarin

  • Concurrent doses ≤ 2 mg/day allowed for prophylaxis of thrombosis
  • Concurrent low molecular weight heparin allowed provided PT INR ≤ 1.5
• No concurrent agents with proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide acetate)
• No concurrent combination antiretroviral therapy for HIV-positive patients