Symptoms and General Pathology

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Thyroid Neoplasms

Thyroid Cancer, Papillary

Thyroid Diseases

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Papillary Thyroid Carcinoma

Thyroid Cancer, Follicular

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Fluorodeoxyglucose F18

Azacitidine

Decitabine

Iodine

Cadexomer iodine

Antimetabolites

Enzyme Inhibitors

Radiopharmaceuticals

Starting dose 6 mg/m\^2 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 participants 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.

Undergo thyrotropin-alfa stimulated radioactive iodine scan

Iodine I 131

Recombinant thyrotropin alfa

Fludeoxyglucose F 18

Positron emission tomography

Steven Sherman

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.

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.

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

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

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.

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.

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.

National Cancer Institute (NCI)

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 participants 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.

Decitabine: 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.

Iodine I 131: Undergo thyrotropin-alfa stimulated radioactive iodine scan

Recombinant thyrotropin alfa: Undergo thyrotropin-alfa stimulated radioactive iodine scan

Treatment

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Participants who received at least one dose of therapy.

Steven I. Sherman, MD / Professor

Per protocol, 1 participant interpreted by local treating investigator as responsive (increased radioiodine uptake on diagnostic scan after therapy), entered second decitabine treatment receiving radioiodine therapeutic dose. Subsequent central review of both scans for formal protocol response interpreted scans as negative for radioiodine uptake.

Restoration of Radioiodine Uptake in Metastatic Lesions as Demonstrated by Diagnostic Whole-body Scanning After Decitabine Administration

Grade 1, Nausea

Grade 1, Fatigue

Grade 1, Oral Mucositis

Grade 1, Pharyngolaryngeal pain

Grade 1, Decreased white blood cell

Grade 2, Fatigue

Grade 2, Decreased white blood cell

Grade 2, Neutrophil count decreased

Grade 2, Lymphocyte count decreased

Grade 3, Decreased white blood cell

Grade 3, Neutrophil count decreased

Grade 3, Febrile neutropenia

Grade 3, Infections

Grade 3, respiratory disorders

Grade 4, Decreased white blood cell

Grade 5

Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

No secondary endpoints were measured as no patient met the primary endpoint. These secondary endpoints would only have been assessed if a patient had met the primary endpoint, restoration of radioiodine uptake to justify radioiodine therapy.

Efficacy of Subsequent Radioiodine Therapy in Terms of CR/PR/SD of Any Radiographic Disease.

Change in Fludeoxyglucose (FDG) Uptake Measured by Positron Emission Tomography in Metastatic Tumor Sites Before and After DNA-methyltransferase Inhibitor Therapy (Optional). No Secondary Endpoints Were Measured as no Patient Met the Primary Endpoint.

Efficacy of Subsequent Radioiodine Therapy in Terms of Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) of Any Radiographic Disease

Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level

Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level.These Secondary Endpoints Would Only Have Been Assessed if a Patient Had Met the Primary Endpoint, Restoration of Radioiodine Uptake to Justify Radioiodine Therapy.

Overall Study

Spots Global Cancer Trial Database for recombinant thyrotropin alfa