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Thyroid CancerPhase 2/3IoNNCT01398085

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

A Phase 2/3 study testing I131 1.1 GBq and No Radioactive iodine (No-RAI) ablation in people with Thyroid Cancer and Thyroid Neoplasms, run by University College, London at 36 sites in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Thyroid Cancer, Thyroid Neoplasms
What is being tested?
I131 1.1 GBq and No Radioactive iodine (No-RAI) ablation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
504 participants
Where
36 sitesUnited Kingdom
Study dates
26 Jun 2012to Mar 2031
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 47Show fewer
  • 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).
  • 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.

Who cannot join

  • 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:
Show all 74Show fewer
  • 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:
  • 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

Trial locations and contacts

36 sites in 1 country.

36 sites in 1 country

United Kingdom36 sites

  • Belfast Health and Social Care Trust

    Belfast, BT9 7AB

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham

  • University Hospitals Sussex NHS Foundation Trust

    Brighton, BN2 5BE

  • University Hospital Bristol NHS Foundation Trust

    Bristol, BS1 3NU

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, CB2 0QQ

  • East Kent Hospitals University NHS Foundation Trust

    Canterbury, CT1 3NG

  • Velindre NHS Trust

    Cardiff, CF15 7QZ

  • Mid and South Essex NHS Foundation Trust

    Chelmsford

  • Gloucestershire Hospitals NHS Trust

    Cheltenham

  • Royal Derby Hospital NHS Foundation Trust

    Derby, DE223NE

  • NHS Lothian

    Edinburgh, EH4 2XU

  • Royal Devon and Exeter Hospital NHS Foundation Trust

    Exeter, EX2 5DW

  • Glasgow and Clyde NHS Trust

    Glasgow, G12 0YN

  • The Royal Surrey County Hospital NHS Foundation Trust

    Guildford, GU1 4JW

  • Hull University Teaching Hospitals NHS Trust

    Hull, HU16 5JU

  • Ipswich Hospital NHS Trust

    Ipswich, IP4 5PD

  • Leeds Teaching Hospitals NHS Trust

    Leeds, LS9 7TF

  • University Hospitals of Leicester NHS Trust

    Leicester, LE1 5WW

  • Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • Imperial College Healthcare NHS Trust

    London, W6 8RF

  • Barts Health NHS Trust

    London

  • Guy's and St Thomas' NHS Foundation Trust

    London

  • University College London Hospitals NHS Foundation Trust

    London

  • Maidstone and Tunbridge Wells NHS Trust

    Maidstone, ME16 9QQ

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • South Tees Hospitals NHS Trust

    Middlesbrough, TS4 3BW

  • Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle, NE7 7DN

  • Norfolk and Norwich University Hospitals NHS Foundation Trust

    Norwich

  • Nottingham University Hospitals NHS Trust

    Nottingham, NG5 1PB

  • University Hospitals Dorset NHS Foundation Trust

    Poole, DT1 2JY

  • Portsmouth Hospitals University NHS Trust

    Portsmouth, PO6 3LY

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield, S10 2SJ

  • Southend University Hospitals NHS Trust

    Southend, SS0 0RY

  • East and North Hertfordshire NHS Trust

    Stevenage, SG1 4AB

  • University Hospitals of North Midlands NHS Trust

    Stoke-on-Trent, ST4 6QG

  • Royal Wolverhampton NHS Trust

    Wolverhampton

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
I131 1.1 GBq, No Radioactive iodine (No-RAI) ablation
Keywords
Papillary thyroid carcinoma, Follicular thyroid carcinoma, Hurthle cell carcinoma of the thyroid, Iodine Radioisotopes
Medical subject headings
Thyroid Neoplasms, Thyroid Cancer, Papillary, Adenocarcinoma, Follicular, Thyroid cancer, Hurthle cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • I131 1.1 GBqRadiation

    Also called Sodium iodide capsule

    Radio-iodine

  • No Radioactive iodine (No-RAI) ablationOther

    No Radioactive iodine (No-RAI) ablation

Study groups in NCT01398085
Study groupRoleWhat they receive
Radioactive iodine (RAI) ablation ArmActive comparatorPatients will be randomised to receive Radioactive iodine (RAI) ablation I131 1.1 GBq
Receives: Radiation: I131 1.1 GBq
No Radioactive iodine (No-RAI) ablationOtherPatients will be randomised to receive No Radioactive iodine (No-RAI) ablation
Receives: Other: No Radioactive iodine (No-RAI) ablation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase II: monthly patient accrual rates

    To determine if recruitment into a phase III trial is feasible

    Measured: Evaluated within months 7-18 of the trial

  2. Phase III: Disease-free thyroid specific survival

    DFS measured from randomisation until date of recurrence or death from thyroid cancer

    Measured: From randomisation until recurrence or death from thyroid cancer

Secondary outcomes (8)

  1. Phase III: Mortality (cause and date of death)

    Cause and date of death

    Measured: From randomisation until death

  2. 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.

    Measured: After follow up is complete (estimated year 8-9 of trial)

  3. 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.

    Measured: After follow up is complete (estimated year 8-9 of trial)

  4. Phase III: Health-related quality of life

    Quality of Life

    Measured: After follow up is complete (estimated year 8-9 of trial)

  5. 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.

    Measured: After follow up is complete (estimated year 8-9 of trial)

  6. 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.

    Measured: After follow up is complete (estimated year 8-9 of trial)

  7. Phase III: Further RAI ablations

    Further RAI ablation and the reasons for this

    Measured: After follow up is complete (estimated year 8-9 of trial)

  8. 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.

    Measured: After follow up is complete (estimated year 8-9 of trial)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2011 (estimated)
  2. Study start26 Jun 2012
  3. Primary completionMar 2031 (estimated)
  4. Study completionMar 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
504 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01398085
Sponsor's protocol ID
UCL/10/0299
Other IDs
2011-000144-21, Cancer Research UK, ISRCTN
Acronym
IoN
Status last verified
May 2026
First submitted
6 Jul 2011
Last updated
7 May 2026
Results posted
No
Data monitoring committee
No

Publications

  • Mallick U, Newbold K, Beasley M, Garcez K, Wadsley J, Johnson SJ, Stephenson T, Gaze M, Goodman A, Jefferies S, Sivabalasingham S, Slevin N, Wilkinson DP, Macias-Fernandez E, Power D, Roques T, Speed L, Nutting C, Mochloulis G, Gerrard G, Candish C, Morgan S, Tripathi D, Truran P, Arthur C, Wieczorek A, Madhavan K, Maclean J, Boote D, Kim D, Pascoe A, Pitiyage G, Forsyth S, Ambrose E, Chang E, Farnell K, Hackshaw A. Thyroidectomy with or without postoperative radioiodine for patients with low-risk differentiated thyroid cancer in the UK (IoN): a randomised, multicentre, non-inferiority trial. Lancet. 2025 Jul 5;406(10498):52-62. doi: 10.1016/S0140-6736(25)00629-4. Epub 2025 Jun 18.

    PubMed 40543520

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing I131 1.1 GBq and No Radioactive iodine (No-RAI) ablation in people with Thyroid Cancer and Thyroid Neoplasms, run by University College, London at 36 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 47 inclusion and 74 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase II: monthly patient accrual rates (time frame: Evaluated within months 7-18 of the trial). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01398085, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.

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