Adjuvant Treatment with High dose versus Low dose of RadioActive Iodine in Intermediate Risk Differentiated Carcinoma of Thyroid with Lymph Node Metastasis - RANDOMIZED OPEN LABEL PHASE 3 NON-INFERIORITY TRIAL
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 580
- 试验地点
- 1
- 主要终点
- Primary endpoint
研究概览
简要总结
About the disease: Most of the thyroid cancers are slowly growing tumors with good survival outcomes and fall in the low risk spectrum. However, patients with thyroid cancer that has spread to the local lymph nodes of the neck usually have poorer outcome. These patients are at a higher risk of future recurrence. However, even in these patients’ survival outcome generally remains unchanged.
The current treatment: The treatment of choice for thyroid cancer with metastatic neck nodes is surgery followed by treatment with Radioactive Iodine or Iodine-131 (RAI). RAI is a radioactive element that when ingested preferentially goes to the thyroid cancer cells. After being localized inside these cells they emit radiation to kill them. Studies have shown that treatment with RAI after surgery decreases the rate of cancer recurrence. This treatment is usually given in an oral formulation (either tablet or liquid) that patient has to swallow. The dose of RAI given varies quite a bit depending on institutions and local practice. Most prevalent practice in India is to give around 100-120 mCi. However, lots of studies have been published that suggest that a lower dose of RAI ( 30 mCi for example) amy be as beneficial as the more conventional higher dose.
The clinical question: Patients who receive high dose of RAI need to be admitted in an isolation ward, separate from everyone for few days till the radiation level in their body comes down to an acceptable level. This can be quite cumbersome for the patients. Also, establishing and operating these isolation wards are not easy and have significant operational hurdles. RAI is a generally well tolerated treatment, however it does have some toxicities which are dose dependent and are more common with higher doses. In recent years lots of studies have been published that suggest that a lower dose of RAI ( 30 mCi for example) may be as beneficial as the more conventional higher dose. 30 mCi RAI give a much lower radiation burden to the patients and can be given on OPD basis. No isolation wards are necessary for this dose of RAI and patients can be discharged on the same day of treatment. Any form of toxicity is virtually non existent with 30 mCi of RAI. Even though studies support the role of 30 mCi RAI in these type of patients, no randomized clinical trials have been published so far. So, we want to conduct a phase 3 randomised trial where we can see if clinical effect of 30 mCi RAI in reducing future recurrence rates is comparable to that of 100-120 mCi RAI.
Primary objective: 1) To see the rate of persistence of cancer or recurrent cancer at the end of 5 year follow up. Secondary objectives; 1) A host of secondary endpoints will be analysed, however most important are; the toxicity profiles of both doses of RAI and number of patients who needed retreatment. These rates will be estimated at the end of 5 year and 7 years. Methodology: The study will take place in Tata Memorial hospital, Mumbai and in ACTREC, Navi Mumbai Patients: Patients with thyroid cancer with nodal metastasis who have undergone surgery will be included in this study. No patients aged <18 years, pregnant or nursing mothers will be included in the study. Number of patients: We are expecting to recruit 580 patients
total Recruitment period: 6 years
Rnadomisation: A computer program will randomly assign patients into two arms: a) Arm A b) Arm B
Follow up: Arm B: 290 patients Patients in this arm will receive 30 mCi RAI Patients of both these arms will be followed up for total 7 years. During this time patients will be put on adequate thyroid hormone supplementation. During follow up routine investigations such as neck USG and some blood tests such as serum TSH, Thyroglobulin and Antithyroglobulin antibody will be done, every year. These tests will help us to detect recurrent cancer. All of these investigations are part of the established standard for thyroid cancer treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Age more than 18
- •Histopathologically proven well differentiated DTC satisfying following criteria a.
- •T1-T3a with cN1 AJCC 8th edition b.
- •Clinically detectable lymph node metastasis c.
- •Metastatic lymph node size less than 3 cm.
排除标准
- •High risk histopathology- tall cell, columnar cell, solid variant, hobnel variant, poorly differentiated, widely invasive follicular carcinoma more than 4 lympho-vascular emboli
- •Gross extrathyroidal extension of tumour
- •Incomplete surgery R1, R2 resection, tumour spill during surgery
- •Any lymphnode size more than or equal to 3 cm
- •Lymphnodes with gross extranodal extension
- •Lymph-node micro metastasis detected in histopathology in the absence of any clinically detectable nodes
- •Distant metastasis indicated by cross sectional imaging or whole body scan or by abnormally high post-operative thyroglobulin
- •Presence of any other malignancy 9.Pregnancy, lactation or nursing mother.
结局指标
主要结局
Primary endpoint
时间窗: Follow up schedule- | follow up 1- 6 months to 1 year from date of treatment | follow up 2- 2 years plus minus 2 months from the date of treatment | follow up 3- 3 years plus minus 2 months from the date of treatment | follow up 4- 4 years plus minus 2 months from the date of treatment | follow up 5- 5 years plus minus 2 months from the date of treatment | follow up 6- 6 years plus minus 2 months from the date of treatment | follow up 7- 7 years plus minus 2 months from the date of treatment
Patients with no evidence of structural disease, Defined as the percentage of patients without persistent or recurrent structural disease at the end of five year follow up. It will include patients with excellent response, indeterminate response and biochemical incomplete response, but are without structural disease at the end of follow up.
时间窗: Follow up schedule- | follow up 1- 6 months to 1 year from date of treatment | follow up 2- 2 years plus minus 2 months from the date of treatment | follow up 3- 3 years plus minus 2 months from the date of treatment | follow up 4- 4 years plus minus 2 months from the date of treatment | follow up 5- 5 years plus minus 2 months from the date of treatment | follow up 6- 6 years plus minus 2 months from the date of treatment | follow up 7- 7 years plus minus 2 months from the date of treatment
次要结局
- Success rate of ablation of thyroid remnant(Follow up period of 5 to 7 years)
- Percentage of patients without persistent or recurrent structural disease with or without rise in Triglycerides at the end of 7 year follow up.(Follow up period of 5 to 7 years)
- Disease free survival Defined as the time duration from the date of randomization to the date of structural recurrence or death due to thyroid cancer.(Follow up period of 5 to 7 years)
- Rate of patients undergoing retreatment with radio iodine at the end of 5 year and 7 years(Follow up period of 5 to 7 years)
- Rate of patients undergoing re surgery at the end of 5 year and 7 year(Follow up period of 5 to 7 years)
- Rate of biochemical incomplete response at the end of 5 year and 7 year(Follow up period of 5 to 7 years)
- Rate of biochemical recurrence in the absence of structural disease, after initial excellent or indeterminate response, at the end of 5 year and 7 year(Follow up period of 5 to 7 years)
- Adverse effects will be assessed with the help of a clinical questionnaire at inclusion, at the time of discharge, at 6 months after radio iodine therapy, at 3 years, 5 years and 7 years from the date of treatment.(Follow up period of 5 to 7 years)
- Fear of cancer recurrence will be evaluated with Fear of Cancer Recurrence - 7 questionnaire at inclusion, at the time of discharge, and respectively at 1 year, 3 year, 5 year and 7 year from the date of treatment.(Follow up period of 5 to 7 years)
研究者
Dr Venkatesh Rangarajan
Tata Memorial Centre