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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase II Study of Decitabine in Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Radioiodine

Brief Summary: This phase II trial is studying how well decitabine works in treating patients with metastatic papillary thyroid cancer or follicular thyroid cancer that has stopped responding to radioactive iodine. Iodine I 131 (radioactive iodine) kills thyroid cancer cells. Metastatic thyroid cancer cells can lose the ability to be treated with radioactive iodine. Decitabine may help thyroid cancer cells regain the ability to respond to treatment with radioactive iodine.

Detailed Summary:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Restoration of Radioiodine Uptake in Metastatic Lesions as Demonstrated by Diagnostic Whole-body Scanning After Decitabine Administration [ Time Frame: Week 3 following 2 weeks of Decitabine therapy ]

Number of participants with restoration of radioiodine responsiveness as determined by visible uptake on radioiodine scan in radiographically detectable metastatic foci of papillary or follicular thyroid carcinoma. Response to Decitabine defined as demonstration of radioiodine uptake determined by centralized blinded review of diagnostic scan. All who demonstrated radioiodine uptake in metastatic foci following decitabine therapy would then undergo thyroid hormone withdrawal and a second course of decitabine in preparation for therapeutic administration of radioiodine.

Diagnostic radioiodine scans following decitabine therapy (week 3) with a radioiodine scan following thyrotropin alfa stimulation, 0.9 mg intramuscular (IM) injection 24 and 48 hours before administration of the 131I for imaging. Whole body scans (WBS) performed using a gamma camera.



Original Primary Outcome:

Current Secondary Outcome:

  • Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level [ Time Frame: 3 months ]
  • Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level [ Time Frame: 6 months ]
  • Efficacy of Subsequent Radioiodine Therapy in Terms of Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) of Any Radiographic Disease [ Time Frame: 3 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
  • Efficacy of Subsequent Radioiodine Therapy in Terms of CR/PR/SD of Any Radiographic Disease [ Time Frame: 6 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
  • Change in Fludeoxyglucose (FDG) Uptake Measured by Positron Emission Tomography (PET) in Metastatic Tumor Sites Before and After DNA-methyltransferase Inhibitor Therapy (Optional) [ Time Frame: Baseline to 3 weeks ]
  • Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: Up to 6 months ]
    Summary of Adverse Events (AEs) by Maximum Grade where Grade 1 AEs >20%, Grade 2 AEs >10%, all Grade 3, Grade 4 and Grade 5 reported.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 10, 2004
Date Started: May 2004
Date Completion:
Last Updated: August 20, 2014
Last Verified: May 2014