Phase II Study of Decitabine in Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Radioiodine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Restoration of Radioiodine Uptake in Metastatic Lesions as Demonstrated by Diagnostic Whole-body Scanning After Decitabine Administration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed papillary thyroid or follicular thyroid carcinoma:
- •Differentiated disease;
- •Metastatic disease documented by ultrasound, computed tomography (CT) scan (without iodinated contrast), or MRI - All metastatic disease foci =< 10 mm in all dimensions
- •Must have been treated with total or near-total thyroidectomy AND at least 1 course of iodine I 131 (131I)(>=29.9 mCi) OR demonstrated negative uptake on a postoperative low-dose131I scan
- •Must have undergone whole body 131I scan 1-3 days after administration of =< 5.5 mCi of 131I demonstrating no visible iodine uptake within the lesions unless demonstrated negative uptake on a postoperative low-dose131I scan within the past 12 weeks:
- •Must have 24-hour urine iodine excretion =< 500 mcg within 1 week of 131I scan
- •Must be receiving thyroid hormone therapy AND have thyroid-stimulating hormone level =< 0.5 mU/L
- •No known brain metastases
- •Performance status:
- •Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100%
- •Hematopoietic:
- •Absolute neutrophil count >= 1,500/mm3;
- •Platelet count >= 100,000/mm3;
- •White Blood Count (WBC) >= 3,000/mm3
- •aspartate aminotransferase-alanine aminotransferase (AST and ALT) =< 2.5 times upper limit of normal;
- •Bilirubin normal
- •Creatinine not elevated OR
- •Creatinine clearance >= 60 mL/min
- •Cardiovascular:
- •No symptomatic congestive heart failure;
- •No unstable angina pectoris;
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior allergic reaction attributed to compounds of similar chemical or biological composition to decitabine
- •No concurrent uncontrolled illness
- •No active or ongoing infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No prior cytotoxic chemotherapy for thyroid cancer
- •At least 6 months since prior external beam radiotherapy administered for locoregional disease in the thyroid bed or to the cervical or upper mediastinal lymph node regions (no more than 6,000 cGy)
- •More than 6 months since other prior radiotherapy and recovered
- •More than 6 months since prior therapeutic 131I > 10 mCi
- •More than 18 months since prior cumulative 131I activity of at least 500 mCi
- •More than 12 months since prior amiodarone (Unless 24-hour urinary iodine excretion is =< 500 mcg)
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent anticancer therapy
- •No other concurrent investigational agents
- •More than 6 months since prior intrathecal iodinated contrast (Unless 24-hour urinary iodine excretion is =< 500 mcg)
- •More than 3 months since prior IV or oral iodinated contrast for radiographic studies (Unless 24-hour urinary iodine excretion is =< 500 mcg)
排除标准
- 未提供
研究组 & 干预措施
Treatment
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.
干预措施: Decitabine (Drug)
Treatment
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.
干预措施: Iodine I 131 (Radiation)
Treatment
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.
干预措施: Recombinant thyrotropin alfa (Biological)
Treatment
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.
干预措施: Fludeoxyglucose F 18 (Radiation)
Treatment
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.
干预措施: Positron emission tomography (Procedure)
结局指标
主要结局
Restoration of Radioiodine Uptake in Metastatic Lesions as Demonstrated by Diagnostic Whole-body Scanning After Decitabine Administration
时间窗: 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.
次要结局
- Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(Up to 6 months)
- Efficacy of Subsequent Radioiodine Therapy in Terms of CR/PR/SD of Any Radiographic Disease.(6 months)
- 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.(Baseline to 3 weeks)
- Efficacy of Subsequent Radioiodine Therapy in Terms of Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) of Any Radiographic Disease(3 months)
- Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level(6 months)
- 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.(3 months)