Phase II Trial of Sunitinib (SU11248) in Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers and Medullary Thyroid Cancers

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