Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Azacitidine to Restore Thyroid Function in Patients With Persistent or Metastatic Thyroid Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	Any age	NCI	UKMC-9700053 NCI-T99-0045, NCT00004062, T99-0045

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.

Entry Criteria

Disease Characteristics:

Radiologically confirmed persistent or metastatic follicular or papillary
thyroid cancer following total thyroidectomy and radioiodine ablation therapy
 Metastatic disease confirmed histologically or cytologically or by elevated
  thyroglobulin levels

No radioiodine uptake by whole body scanning

Stable iodine contamination from radiologic contrast material within the past
10 months allowed, if absence of current contamination demonstrated by less
than 80 micrograms of iodine in a 24 hour urine collection
 

Prior/Concurrent Therapy:

At least 4 weeks since prior levothyroxine

Any prior therapy for restoration of radioiodine uptake allowed, if
unsuccessful and did not exceed treatment schedules planned for this study
 

Patient Characteristics:

Age:
 Any age

Performance status:
 Not specified

Life expectancy:
 Not specified

Hematopoietic:
 Absolute neutrophil count at least 1,500/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 SGOT/SGPT no greater than 2.5 times upper limit of normal (ULN)
 Bilirubin no greater than 1.5 times ULN

Renal:
 Creatinine no greater than 1.5 times ULN OR
 Creatinine clearance at least 50 mL/min

Other:
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Lucille P. Markey Cancer Center at University of Kentucky

Kenneth Ain, MD, Protocol chair		Ph: 859-323-3778 Email: Kbain1@email.uky.edu

Registry Information
Official Title		Restoration of Radioiodine Uptake in Thyroid Carcinoma: A Clinical Trial
Trial Start Date		1999-07-16
Registered in ClinicalTrials.gov		NCT00004062
Date Submitted to PDQ		1999-08-06
Information Last Verified		2004-05-12