Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer

PRIMARY OBJECTIVES:

I. Evaluate the response of sunitinib (sunitinib malate) per Response Evaluation Criteria in
Solid Tumors (RECIST) criteria in patients with recurrent/metastatic iodine refractory well
differentiated thyroid carcinoma (WDTC) or medullary thyroid carcinoma (MTC).

SECONDARY OBJECTIVES:

I. Evaluate early positron emission tomography (PET) changes in patients with WDTC and MTC
treated with sunitinib.

II. Determine the safety and toxicity of sunitinib given as a continuous treatment in
patients with WDTC and MTC.

III. Evaluate the effect of sunitinib therapy on overall survival, duration of response and
time-to-progression.

IV. Evaluate serial tumor markers, thyroglobulin (WDTC) or calcitonin (MTC), during therapy.
These measurements will not be used to define disease progression or response.

V. Correlate changes in serial tumor markers with radiologic response.

OUTLINE:

Patients receive sunitinib malate orally (PO) once daily (QD). Treatment continues in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then for 2
years.

Inclusion Criteria:

- Histologically or cytologically proven metastatic WDTC or MTC

- Evidence of refractoriness to iodine therapy for WDTC documented by a combination of
imaging and thyroglobulin or by biopsy

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3

- Evidence of fludeoxyglucose F 18 (FDG) PET avid metastatic tumors

- Measurable disease by RECIST criteria

- Resolution of all acute toxic effects of prior systemic therapy (including iodine
therapy or chemotherapy), radiotherapy or surgical procedure to National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
grade =< 1

- Total serum bilirubin =< 1.5 x upper limit of normal (ULN) (patients with Gilbert's
disease exempt)

- Serum transaminases =< 2.5 x ULN or =< 5.0 X ULN if secondary to liver metastases

- Serum creatinine =< 1.5 x ULN

- Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

- Platelets >= 100,000/uL

- Hemoglobin >= 9.0 g/dL

- Willingness and ability to comply with scheduled visits, treatment plans and
laboratory tests and other study procedures

- Male and female patients with reproductive potential must use an acceptable
contraceptive method

- Signed and dated informed consent document indicating that the patient has been
informed of all the pertinent aspects of the trial prior to enrollment

Exclusion Criteria:

- Concomitant treatment in another therapeutic clinical trial

- ECOG performance status >= 3

- Symptomatic, untreated, brain metastasis

- Second primary malignancy that is clinically detectable or clinically significant at
the time of consideration for study enrollment

- Full-dose anticoagulation defined as:

- Low molecular weight heparin use with the intent of full dose anticoagulation;
example: enoxaparin 1.5 mg/kg daily or equivalent

- Warfarin use to keep international normalized ratio (INR) greater than or equal
to 2

- History of gross hemoptysis (defined as bright red blood of at least 1/2 teaspoon or
2.5 mL per episode) within 3 months prior to study drug administration unless
definitively treated with surgery or radiation

- Any of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident or transient
ischemic attack, or pulmonary embolism; ongoing cardiac dysrhythmias of NCI CTCAE
Version 3.0 grade >= 2

- Type I Diabetes Mellitus; patients with Type II Diabetes Mellitus will be included as
long as their glucose can be controlled between levels of 80 and 150 mg/dL

- Uncontrolled Hypertension (> 150/100 mm Hg despite optimal medical therapy)

- Major surgery or radiation therapy within 4 weeks of starting the study treatment

- Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that would impart, in the judgment of the investigator, excess risk
associated with study participation or study drug administration, or which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study

- Pregnancy or breast feeding