Trial Information

Restoration of Radioiodine Uptake in Thyroid Carcinoma: A Clinical Trial

OBJECTIVES: I. Determine the ability of azacitidine to restore iodine uptake by
dedifferentiated thyroid cancer, enabling detection and treatment with iodine I 131 in
patients with metastatic follicular or papillary thyroid cancer. II. Evaluate different
doses and schedules of azacitidine administration to determine an optimally effective
combination for restoration of iodine I 131 uptake with acceptable toxicity in this patient
population. III. Determine the efficacy of azacitidine plus iodine I 131 in this patient
population.

OUTLINE: This is a dose escalation study of azacitidine. Patients undergo a control phase
consisting of oral liothyronine sodium twice daily on weeks 1-4 and a low iodine diet on
weeks 4-7. At week 6, patients receive a scan dose of iodine I 131 followed by whole body
scanning over 5 days. Beginning at week 7, patients undergo a treatment phase consisting of
oral liothyronine sodium twice daily for 3 weeks, azacitidine subcutaneously daily for 10 or
20 days (weeks 7-11) and a low iodine diet on weeks 8-11. During week 11, patients undergo
additional whole body scanning over 5 days followed by a therapeutic dose of iodine I 131.
Patients achieving successful therapy receive 5 additional doses of azacitidine. Cohorts of
4 patients receive escalating doses of azacitidine until demonstrable radioiodine uptake is
seen or the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 8 patients experience dose limiting toxicity. Patients are
followed weekly for 8 weeks.

PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study.