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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid Cancer
• Intervention / Treatment: Radiation: I131 1.1 GBq

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 504
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • University Hospitals Birmingham NHS Foundation Trust
  • Brighton, United Kingdom, BN2 5BE
    • Brighton and Sussex University Hospitals NHS Trust
  • Bristol, United Kingdom, BS1 3NU
    • University Hospital Bristol NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Canterbury, United Kingdom, CT1 3NG
    • East Kent Hospitals University NHS Foundation Trust
  • Chelmsford, United Kingdom
    • Mid Essex Hospitals Services NHS Trust
  • Cheltenham, United Kingdom
    • Gloucestershire Hospitals NHS Trust
  • Derby, United Kingdom, DE223NE
    • Royal Derby hospital NHS foundation trust
  • Edinburgh, United Kingdom, EH4 2XU
    • NHS Lothian
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter NHS Trust
  • Glasgow, United Kingdom, G12 0YN
    • Glasgow and Clyde NHS Trust
  • Guildford, United Kingdom, GU1 4JW
    • The Royal Surrey County Hospital NHS Foundation Trust
  • Ipswich, United Kingdom, IP4 5PD
    • Ipswich Hospital NHS Trust
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Teaching Hospitals NHS Trust
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester NHS Trust
  • London, United Kingdom
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom
    • Barts Health NHS Trust
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden NHS Foundation Trust
  • London, United Kingdom, W6 8RF
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom
    • Guys and St Thomas' NHS Foundation Trust
  • Maidstone, United Kingdom, ME16 9QQ
    • Maidstone and Tunbridge Wells NHS Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Middlesbrough, United Kingdom, TS4 3BW
    • South Tees Hospitals NHS Trust
  • Nantgarw, United Kingdom, CF15 7QZ
    • Velindre NHS Trust
  • Newcastle, United Kingdom, NE7 7DN
    • Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospitals NHS Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust
  • Portsmouth, United Kingdom
    • Portsmouth Hospitals NHS Trust
  • Sheffield, United Kingdom, S10 2SJ
    • Sheffield Teaching Hospitals NHS Foundation Trust
  • Southend, United Kingdom, SS0 0RY
    • Southend University Hospitals NHS Trust
  • Stevenage, United Kingdom, SG1 4AB
    • East and North Herts
  • Wolverhampton, United Kingdom
    • Royal Wolverhampton Nhs Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Cancer Research UK
• Investigators: Principal Investigator: Ujjal Mallick, MBBS, Master of Surgery, FRCR, Newcastle-upon-Tyne Hospitals NHS Foundation Trust

Publications and helpful links

Helpful Links

• Cancer Research UK & UCL Cancer Trials Centre website

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: July 6, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (Estimated): July 20, 2011

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Papillary thyroid carcinoma; Follicular thyroid carcinoma; Hurthle cell carcinoma of the thyroid; Iodine Radioisotopes
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: UCL/10/0299; ISRCTN (Registry Identifier: ISRCTN11460478); 2011-000144-21 (EudraCT Number); Cancer Research UK (Other Grant/Funding Number: CRUK/11/010)