Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

Inclusion Criteria:

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

  • Well-differentiated thyroid carcinoma (WDTC), including any of the following subtypes:

    • Papillary
    • Follicular
    • Hürthle cell
  • Medullary thyroid carcinoma (MTC)
• Must show evidence of disease progression within the past 6 months despite treatment with iodine I 131 therapy OR ineligible for iodine I 131 therapy
• Unresectable disease
• Patients with WDTC must be receiving thyroxine suppression therapy

• Measurable disease meeting 1 of the following criteria:

  • Radiographically measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
  • Biochemically measurable disease defined as an elevated thyroglobulin (WDTC patients) or calcitonin (MTC patients)

• No known brain metastases

  • Patients with brain metastases with stable neurologic status after local therapy (surgery or radiotherapy) for ≥ 8 weeks from definitive therapy and without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events are eligible
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Calcium ≤ 12.0 mg/dL
• Bilirubin normal
• AST or ALT ≤ 2.5 times upper limit of normal (ULN) (or ≤ 5.0 times ULN if patient has liver metastases)
• Creatinine normal OR creatinine clearance ≥ 60 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
• No poorly controlled hypertension, defined as systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg

• No condition that would impair ability to swallow and retain sunitinib malate tablets, including any of the following:

  • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement of IV alimentation
  • Prior surgical procedures affecting absorption
  • Active peptic ulcer disease
• No serious or nonhealing wound, ulcer, or bone fracture
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No pulmonary embolism within the past 12 months
• QTc < 500 msec
• No significant ECG abnormalities
• No cerebrovascular accident or transient ischemic attack within the past 12 months
• No myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic congestive heart failure, or coronary or peripheral artery bypass graft or stenting within the past 12 months
• No New York Heart Association (NYHA) class III-IV heart failure or other condition
• No serious ventricular arrhythmia (i.e., ventricular fibrillation or ventricular tachycardia ≥ 3 beats in a row)

• Patients with any of the following conditions must have NYHA class II cardiac function confirmed on baseline ECHO/MUGA scan

  • History of class II heart failure and asymptomatic on treatment
  • Prior anthracycline exposure
  • Received central thoracic radiation that included the heart in the radiotherapy port

• No uncontrolled intercurrent illness, including, but not limited to, any of the following:

  • Ongoing or active infections
  • Psychiatric illness or social situation that would preclude study compliance
• Recovered from prior therapy
• No more than 1 prior chemotherapy regimen for metastatic disease
• No prior external-beam radiation to the measured tumor constituting the target lesion(s)
• No prior receptor tyrosine kinase inhibitors
• No prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, VEGF Trap)
• At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• At least 4 weeks since prior major surgery
• No other concurrent anticancer agents or therapies
• No other concurrent investigational agents

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

  • Doses ≤ 2 mg daily for prophylaxis of thrombosis allowed
  • Low molecular weight heparin allowed provided PT INR ≤ 1.5
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent enzyme-inducing anticonvulsants

• No concurrent agents with proarrhythmic potential, including any of the following:

  • Terfenadine
  • Quinidine
  • Procainamide
  • Disopyramide
  • Sotalol
  • Probucol
  • Bepridil
  • Haloperidol
  • Risperidone
  • Indapamide
  • Flecainide

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

  • Azole antifungals (e.g., ketoconazole, itraconazole)
  • Clarithromycin, erythromycin
  • Diltiazem
  • Verapamil
  • HIV-protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir)
  • Delavirdine

• At least 12 days since prior and no concurrent inducers of CYP3A4, including any of the following:

  • Rifampin
  • Rifabutin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • Hypericum perforatum (St. John's wort)
  • Efavirenz
  • Tipranavir