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Study Summary
No. 2003-0308:.......Endocrine; Thyroid......Steven I. Sherman......Endocrine Neoplasia & Hormonal Disorders
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Study Summary Title
Study Summary
Number:
2003-0308
Study Title:Phase II Study of Decitabine in Patients with Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Radioiodine (NCI Protocol #5954)
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Physician New Patient Referral
Name:Steven I. ShermanPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Endocrine Neoplasia & Hormonal DisordersReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2841
Contact us about clinical trials
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General Information
Disease Group:Endocrine
Thyroid
Supported By:N/A
Phase of Study:Phase IIReturn
Visit:
For those who respond to decitabine therapy, 35 days/visits. For those who do
not respond to decitabine therapy, 18 days/visits.
Treatment
Agents:
DecitabineHome Care:None.
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
Patients who respond to decitabine therapy will require hospitalization to
receive radioiodine therapy, as per standard of care, typically lasting 2-3
days.
Description/
Intervention:
The goal of this clinical research study is to find out if treatment with a new
drug, decitabine, can change thyroid cancers that no longer respond to
radioactive iodine treatment, so that they can be effectively treated with
radioactive iodine.
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Study Objectives / Outcomes
1.1. Primary Objective:
        To determine if decitabine can restore radioiodine uptake in metastatic lesions of papillary thyroid cancer or follicular thyroid cancer that are undetectable by low-dose radioiodine scanning.

1.2. Secondary Objectives:
        a) To determine the efficacy of radioiodine therapy administered following restoration of radioiodine uptake in metastatic lesions by decitabine.
        b) To determine the effect of decitabine on clinical and molecular markers of thyroid cancer cell differentiation.
        c) To evaluate the safety and tolerability of decitabine in patients with thyroid cancer while undergoing thyroid hormone withdrawal-induced hypothyroidism and radioiodine therapy
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Study Status Information
Study Activation / Registration Date:05/03/2004
IRB Review and Approval Date:11/05/2003
Study Type:Therapeutic
Recruitment Status:Closed
Projected Accrual:37
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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.

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Links
Registration Number: NCT00085293
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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