IoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients

Study Overview
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Brief Summary
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IoN is a phase II/ III trial that will look to ascertain whether or not radio-iodine ablation is necessary for low risk differentiated thyroid cancer patients.

Detailed Description
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Phase II: to determine if recruitment into a phase III trial is feasible, with a target of 10 patients per month during a minimum of 6 months (evaluated within months 7-18 of the trial). Phase III: to determine whether the 5-year disease-free survival rate among patients who do not have routine Radioactive iodine (RAI) ablation is non-inferior to those who do.

Official Title
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Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients

Conditions
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Thyroid Cancer

Intervention / Treatment
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* Radiation: I131 1.1 GBq


Participation Criteria
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Eligibility Criteria
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TNM eligibility is assessed against TNM7 (7th edition 2009) or TNM8 (8th edition 2017, in use in the UK from 01/01/2018). Eligibility Criteria using TNM7: Inclusion criteria: Histological confirmation of well differentiated thyroid carcinoma: MDT decision for inclusion based on overall clinico-pathological assessment is critical. R0 total thyroidectomy (in one or two stages, no residual disease present; Rx at the discretion of the MDT) within the last 6 months Negative pregnancy test in women of child bearing potential Aged 16 or over WHO performance status 0 - 2, self-caring Histological confirmation of differentiated thyroid carcinoma:MDT decision for inclusion based on overall clinico-pathological assessment Papillary thyroid cancer (PTC): Non aggressive histological features (small foci of aggressive histology allowed at the discretion of the MDT) pT1a (≤1cm) unifocal with positive level VI lymph nodes (pN1a) pT1a(m): all individual foci ≤1cm pT1b and pT1b(m): >1-2cm pT2 and pT2(m): >2-4cm pT3 and pT3(m): >4cm confined to the thyroid pT3 R0 +/- (m): any size with minimal ETE if recommended by the MDT pN0 pN1a pNX Follicular thyroid cancer (FTC) (including oncocytic or Hürthle cell cancer): o minimally invasive FTC -which are considered low risk and are recommended by the specialist MDT based on overall clinico-pathological assessment pT1b and pT2: >1-4cm intrathyroidal pT3 R0:any size up to 4 cm with minimal ETE if recommended by the MDT Histological material available for Central Review (see section 9.7) Willing to use contraception for the duration of the trial until 6 months post radioiodine treatment (for females) or 4 months post treatment (for males) (see section 6.4.2), if allocated to the ablation group. NB: Multifocal tumours (≥2 foci) of all histological types should be designated with (m), and the size of the largest focus determines the classification (as described in the TNM 7th edition). For example, if there are two foci, one 0.8cm and the other 3cm, the classification is based on the 3cm focus; i.e. pT2(m). Exclusion criteria: pT1a - Papillary and Follicular carcinoma which is unifocal and ≤1cm in size, without any positive nodes or unfavourable clinical features, treated by lobectomy. Up to 4cm non-invasive Encapsulated Follicular Variant of Papillary Thyroid Cancer (eFVPTC) with no capsular or vascular invasion (>4 cm can be included at the discretion of the MDT) non-invasive follicular tumour with papillary-like nuclei (NIFTP) Anaplastic, poorly differentiated or medullary carcinoma R1 or R2 thyroidectomy Patients with: pN1b M1 Aggressive Papillary thyroid cancer with any of the following features: Widely invasive Poorly differentiated Anaplastic Tall cell Columnar cell Diffuse sclerosing variants Follicular thyroid cancer/Hürthle cell cancer with any of the following features: Tumours greater than 4cm Widely invasive Poorly differentiated Anaplastic Incomplete resection or lobectomy pT4a and pT4b or macroscopic and microscopic tumour invasion of loco-regional tissues or structures Pregnant women or women who are breast feeding Patients who have had CT performed with iv contrast less than 2-3 months before ablation Previous treatment for thyroid cancer (except surgery in last 6 months) Previous malignancies with limited life expectancy or likely to interfere with the patient's ability to be able to comply with treatment and/or follow-up for at least 5 years The following GI conditions: dysphagia, oesophageal stricture, active gastritis, gastric erosions, peptic ulcer, suspected reduced gastrointestinal motility MDT decision against ablation or suitability for trial in light of severe co-morbid condition/s including: Unstable angina Recent myocardial infarction or cerebrovascular accident (CVA) Severe labile hypertension Any patient who cannot comply with radiation protection including: patients with learning difficulties patients with dementia patients with a tracheostomy that require nursing care patients requiring frequent nursing/ medical supervision Eligibility Criteria using TNM8: Inclusion criteria: Histological confirmation of well differentiated thyroid carcinoma: MDT decision for inclusion based on overall clinico-pathological assessment is critical. R0 total thyroidectomy (in one or two stages, no residual disease present; Rx at the discretion of the MDT) within the last 6 months Negative pregnancy test in women of child bearing potential Aged 16 or over WHO performance status 0 - 2, self-caring Histological confirmation of differentiated thyroid carcinoma:MDT decision for inclusion based on overall clinico-pathological assessment Papillary thyroid cancer (PTC): Non aggressive histological features (small foci of aggressive histology allowed at the discretion of the MDT) pT1a (≤1cm) unifocal with positive level VI lymph nodes (pN1a) pT1a(m): all individual foci ≤1cm pT1b and pT1b(m): >1-2cm pT2 and pT2(m): >2-4cm pT3a and pT3a(m): >4cm confined to thyroid pT1a/1b/2/3 (where minimal microscopic extra thyroidal extension (ETE) does not change the T score) +/- (m): any size with minimal ETE if recommended by the MDT pN0 pN1a pNX Follicular thyroid cancer (FTC) (including oncocytic or Hürthle cell cancer): o minimally invasive FTC -which are considered low risk and are recommended by the specialist MDT based on overall clinico-pathological assessment pT1b and pT2: >1-4cm intrathyroidal pT1a/1b/2/3a (where minimal microscopic ETE does not change the T score): any size up to 4 cm with minimal ETE if recommended by the MDT Histological material available for Central Review (see section 9.7) Willing to use contraception for the duration of the trial until 6 months post radioiodine treatment (for females) or 4 months post treatment (for males) (see section 6.4.2), if allocated to the ablation group. Exclusion criteria: pT1a - Papillary and Follicular carcinoma which is unifocal and ≤1cm in size, without any positive nodes or unfavourable clinical features, treated by lobectomy. Up to 4cm non-invasive Encapsulated Follicular Variant of Papillary Thyroid Cancer (eFVPTC) with no capsular or vascular invasion (>4 cm can be included at the discretion of the MDT) non-invasive follicular tumour with papillary-like nuclei (NIFTP) Anaplastic, poorly differentiated or medullary carcinoma R1 or R2 thyroidectomy Patients with: pN1a with level VII involvement pN1b M1 Aggressive Papillary thyroid cancer with any of the following features: Widely invasive Poorly differentiated Anaplastic Tall cell Columnar cell Diffuse sclerosing variants Follicular thyroid cancer/Hürthle cell cancer with any of the following features: Tumours greater than 4cm Widely invasive Poorly differentiated Anaplastic Incomplete resection or lobectomy pT3b, pT4a and pT4b or macroscopic and microscopic tumour invasion of loco-regional tissues or structures Pregnant women or women who are breast feeding Patients who have had CT performed with iv contrast less than 2-3 months before ablation Previous treatment for thyroid cancer (except surgery in last 6 months) Previous malignancies with limited life expectancy or likely to interfere with the patient's ability to be able to comply with treatment and/or follow-up for at least 5 years The following GI conditions: dysphagia, oesophageal stricture, active gastritis, gastric erosions, peptic ulcer, suspected reduced gastrointestinal motility MDT decision against ablation or suitability for trial in light of severe co-morbid condition/s including: Unstable angina Recent myocardial infarction or cerebrovascular accident (CVA) Severe labile hypertension Any patient who cannot comply with radiation protection including: patients with learning difficulties patients with dementia patients with a tracheostomy that require nursing care patients requiring frequent nursing/ medical supervision

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radioactive iodine (RAI) ablation Arm<br>Patients will be randomised to receive Radioactive iodine (RAI) ablation I131 1.1 GBq | Radiation: I131 1.1 GBq<br>* Radio-iodine<br>* Other names: Sodium iodide capsule;|
| No Intervention: No Radioactive iodine (No-RAI) ablation<br>Patients will be randomised to receive No Radioactive iodine (No-RAI) ablation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: monthly patient accrual rates | To determine if recruitment into a phase III trial is feasible | Evaluated within months 7-18 of the trial | 
| Phase III: Disease-free thyroid specific survival | DFS measured from randomisation until date of recurrence or death from thyroid cancer | From randomisation until recurrence or death from thyroid cancer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase III: Mortality (cause and date of death) | Cause and date of death | From randomisation until death | 
| Phase III: Occurrence of loco-regional recurrence or metastatic disease | Both groups will be compared to ascertain if radio-iodine results in a statistically significant reduction in risk in developing loco-regional recurrence in the low risk subgroup of patients. | After follow up is complete (estimated year 8-9 of trial) | 
| Phase III: Stage of cancer at the time of recurrence, and the ability to treat this successfully | Both groups will be compared to ascertain if radio-iodine results in a statistically significant difference in the stage of cancer at the time of recurrence, and the ability to treat this successfully. | After follow up is complete (estimated year 8-9 of trial) | 
| Phase III: Health-related quality of life | Quality of Life | After follow up is complete (estimated year 8-9 of trial) | 
| Phase III: Adverse events for all patients | Adverse events will be collected for patients in both groups during treatment and the groups compared during analysis. | After follow up is complete (estimated year 8-9 of trial) | 
| Phase III: Further neck surgery | The number of further neck surgeries will be collected for patients in both groups during follow up and the groups compared during analysis. | After follow up is complete (estimated year 8-9 of trial) | 
| Phase III: Further RAI ablations | Further RAI ablation and the reasons for this | After follow up is complete (estimated year 8-9 of trial) | 
| Phase III: Cost-effectiveness | Costs of treatment for both groups will be collected for duration of trial to see if there is a difference between the two. | After follow up is complete (estimated year 8-9 of trial) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Papillary thyroid carcinoma, Follicular thyroid carcinoma, Hurthle cell carcinoma of the thyroid, Iodine Radioisotopes