Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: 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.

PURPOSE: 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.

Further Study Information

OBJECTIVES:

Primary

• 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

• Determine the efficacy of ^131I therapy, administered after restoration of ^131I uptake by decitabine, in these patients.

• Determine the effect of decitabine on clinical and molecular markers of thyroid cancer cell differentiation in these patients.

• 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 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 months.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 4-18.5 months.

Eligibility Criteria

Inclusion Criteria:

1. Histologically confirmed differentiated thyroid carcinoma (papillary or follicular type).

2. Previously been treated with total or near-total thyroidectomy. Must have been treated with at least one course of 131I, or demonstrated negative uptake on a low-dose 131I scan post-operatively. External beam radiotherapy may have previously been administered for locoregional disease in the thyroid bed, or cervical or upper mediastinal lymph node regions, but must have been completed at least 6 months prior to entry.

3. Metastatic disease radiographically documented but must measure 10 mm or less.

4. Within 12 weeks of entry, must have undergone a whole body radioiodine scan one to three days following administration 131I that demonstrates no visible uptake in the metastatic lesions, unless demonstrated negative uptake on a low-dose 131I scan post-operatively. Patients should have undergone the scan following administration of a two dose regimen of thyrotropin alfa. Within one week of the negative radioiodine scan, patients must have had a 24 hr urine iodine excretion demonstrated to be no more than 500 mcg, thereby avoiding a possible false-negative scan due to iodine excess.

5. Must be receiving thyroid hormone therapy with a documented serum TSH level less than or equal to 0.5 mU/L within 4 weeks of study entry, without an intervening change in the prescribed dosage of thyroid hormone therapy

6. Age at least 18 years.

7. ECOG performance status less than or equal to 2 (Karnofsky at least 60%).

8. Patients must have normal organ and marrow function as defined below demonstrated within 4 weeks of study entry: Leukocytes at least 3,000/microliter ANC at least 1,500/microliter platelets at least 100,000/microliter, total bilirubin not more than institutional upper limit of normal, AST(SGOT)/ALT(SGPT) not more than 2.5 X institutional upper limit of normal, creatinine not more than institutional upper limit of normal OR creatinine clearance at least 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

9. The effects of decitabine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because DNA hypomethylating agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

10. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients who have had any cytotoxic chemotherapy for thyroid carcinoma.

2. Patients who have had radiotherapy within 6 months prior to entering the study or those who have not recovered from adverse events due to radiotherapy administered more than 6 months earlier.

3. Patients who have received a therapeutic administration of 131I >10 mCi within the past 6 months, or who have received a cumulative activity of at least 500 mCi within the past 18 months, to minimize the potential adverse effects on bone marrow.

4. Patients who have received intravenous or oral iodinated contrast for radiographic studies within the past 3 months, intrathecal iodinated contrast within the past 6 months, or amiodarone within the past 12 months are excluded because of the risk of false-negative radioiodine scanning, unless a 24 hour urinary iodine excretion is documented to be less than or equal to 500 mcg.

5. Patients may not be receiving any other investigational agents.

6. Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine.

8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

9. Pregnant women are excluded because decitabine is an antimetabolite and DNA hypomethylating agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with decitabine, breastfeeding should be discontinued if the mother is treated with decitabine. Additionally, radioiodine is teratogenic and contraindicated in women who are pregnant. Radioiodine is also contraindicated in breast feeding women.

10. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with decitabine.

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Steven I. Sherman

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00085293
Information obtained from ClinicalTrials.gov on December 15, 2011

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