Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

PRIMARY OBJECTIVE:

I. Determine whether decitabine can restore iodine I 131 (131I) uptake in patients with
metastatic papillary thyroid or follicular thyroid cancer lesions that are undetectable by
low-dose iodine 131I scanning.

SECONDARY OBJECTIVES:

I. Determine the efficacy of 131I therapy, administered after restoration of 131I uptake by
decitabine, in these patients.

II. Determine the effect of decitabine on clinical and molecular markers of thyroid cancer
cell differentiation in these patients.

III. Determine the safety and tolerability of decitabine in patients undergoing thyroid
hormone withdrawal-induced hypothyroidism and 131I therapy.

OUTLINE: This is an open-label, multicenter study.

Patients receive decitabine intravenous (IV) over 1 hour on days 1-5 and 8-12 of weeks 1 and
2 (course 1). On week 3, patients undergo iodine I 131 (131I) scanning using thyrotropin alfa
injections. Patients whose scan does not demonstrate iodine uptake continue suppressive
thyroid hormone therapy but receive no further study therapy. These patients undergo study
follow up.

Patients whose scan demonstrates iodine uptake undergo thyroid hormone withdrawal on weeks
4-8 and receive a second course of decitabine (as in course 1) on weeks 7 and 8. Patients
then receive 131I therapy on week 9.

Patients are followed at 3 and 6 months.

Inclusion Criteria:

- Histologically confirmed papillary thyroid or follicular thyroid carcinoma:

- Differentiated disease;

- Metastatic disease documented by ultrasound, computed tomography (CT) scan
(without iodinated contrast), or MRI - All metastatic disease foci =< 10 mm
in all dimensions

- Must have been treated with total or near-total thyroidectomy AND at least 1 course of
iodine I 131 (131I)(>=29.9 mCi) OR demonstrated negative uptake on a postoperative
low-dose131I scan

- Must have undergone whole body 131I scan 1-3 days after administration of =< 5.5 mCi
of 131I demonstrating no visible iodine uptake within the lesions unless demonstrated
negative uptake on a postoperative low-dose131I scan within the past 12 weeks:

- Must have 24-hour urine iodine excretion =< 500 mcg within 1 week of 131I scan

- Must be receiving thyroid hormone therapy AND have thyroid-stimulating hormone level
=< 0.5 mU/L

- No known brain metastases

- Performance status:

- Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100%

- Hematopoietic:

- Absolute neutrophil count >= 1,500/mm3;

- Platelet count >= 100,000/mm3;

- White Blood Count (WBC) >= 3,000/mm3

- Hepatic:

- aspartate aminotransferase-alanine aminotransferase (AST and ALT) =< 2.5 times
upper limit of normal;

- Bilirubin normal

- Renal:

- Creatinine not elevated OR

- Creatinine clearance >= 60 mL/min

- Cardiovascular:

- No symptomatic congestive heart failure;

- No unstable angina pectoris;

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior allergic reaction attributed to compounds of similar chemical or biological
composition to decitabine

- No concurrent uncontrolled illness

- No active or ongoing infection

- No psychiatric illness or social situation that would preclude study compliance

- No prior cytotoxic chemotherapy for thyroid cancer

- At least 6 months since prior external beam radiotherapy administered for locoregional
disease in the thyroid bed or to the cervical or upper mediastinal lymph node regions
(no more than 6,000 cGy)

- More than 6 months since other prior radiotherapy and recovered

- More than 6 months since prior therapeutic 131I > 10 mCi

- More than 18 months since prior cumulative 131I activity of at least 500 mCi

- More than 12 months since prior amiodarone (Unless 24-hour urinary iodine excretion is
=< 500 mcg)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer therapy

- No other concurrent investigational agents

- More than 6 months since prior intrathecal iodinated contrast (Unless 24-hour urinary
iodine excretion is =< 500 mcg)

- More than 3 months since prior IV or oral iodinated contrast for radiographic studies
(Unless 24-hour urinary iodine excretion is =< 500 mcg)