Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131
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.
Recurrent Thyroid Cancer
Stage IVA Follicular Thyroid Cancer
Stage IVA Papillary Thyroid Cancer
Stage IVB Follicular Thyroid Cancer
Stage IVB Papillary Thyroid Cancer
Stage IVC Follicular Thyroid Cancer
Stage IVC Papillary Thyroid Cancer
Radiation: Iodine I 131
Biological: Recombinant Thyrotropin Alfa
Radiation: Fludeoxyglucose F 18
Procedure: Positron Emission Tomography
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Decitabine in Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Radioiodine|
- Restoration of radioiodine uptake in metastatic lesions as demonstrated by diagnostic whole-body scanning after decitabine administration [ Time Frame: Week 3 ] [ Designated as safety issue: No ]Evaluated for response during 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.
- Efficacy of subsequent radioiodine therapy in terms of change in serum thyroglobulin level [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Efficacy of subsequent radioiodine therapy in terms of change in serum thyroglobulin level [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2004|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Decitabine intravenous (IV) over 1 hour on days 1-5 and 8-12 of weeks 1 and 2 (course 1). Week 3, Iodine I 131 (131I) scanning using thyrotropin alfa injections. Participants whose scan do not demonstrate iodine uptake continue suppressive thyroid hormone therapy but no further study therapy; these who do show uptake undergo thyroid hormone withdrawal on weeks 4-8 and second course of decitabine (as in course 1) on weeks 7 and 8, with 131I therapy on week 9.
Starting dose 6 mg/m^2 intravenously over 1 hour every day for 5 successive days for 2 weeks (10 doses), with possible second course.
Other Name: DacogenRadiation: Iodine I 131
Undergo thyrotropin-alfa stimulated radioactive iodine scan
Other Name: 131IBiological: Recombinant Thyrotropin Alfa
Undergo thyrotropin-alfa stimulated radioactive iodine scanRadiation: Fludeoxyglucose F 18
Optional correlative studiesProcedure: Positron Emission Tomography
Optional correlative studies
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.
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.
|United States, Colorado|
|University of Colorado at Denver Health Sciences Center|
|Aurora, Colorado, United States, 80045|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Steven Sherman, MD||UT MD Anderson Cancer Center|