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

NCT ID: NCT01398085

Last Updated: 2024-05-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

504 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2031-03-31

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.

Conditions

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Thyroid Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radioactive iodine (RAI) ablation Arm

Patients will be randomised to receive Radioactive iodine (RAI) ablation I131 1.1 GBq

Group Type ACTIVE_COMPARATOR

I131 1.1 GBq

Intervention Type RADIATION

Radio-iodine

No Radioactive iodine (No-RAI) ablation

Patients will be randomised to receive No Radioactive iodine (No-RAI) ablation

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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I131 1.1 GBq

Radio-iodine

Intervention Type RADIATION

Other Intervention Names

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Sodium iodide capsule

Eligibility Criteria

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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).


* 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:

* 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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ujjal Mallick, MBBS, Master of Surgery, FRCR

Role: PRINCIPAL_INVESTIGATOR

Newcastle-upon-Tyne Hospitals NHS Foundation Trust

Locations

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University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Brighton and Sussex University Hospitals NHS Trust

Brighton, , United Kingdom

Site Status

University Hospital Bristol NHS Foundation Trust

Bristol, , United Kingdom

Site Status

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

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East Kent Hospitals University NHS Foundation Trust

Canterbury, , United Kingdom

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Mid Essex Hospitals Services NHS Trust

Chelmsford, , United Kingdom

Site Status

Gloucestershire Hospitals NHS Trust

Cheltenham, , United Kingdom

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Royal Derby hospital NHS foundation trust

Derby, , United Kingdom

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NHS Lothian

Edinburgh, , United Kingdom

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Royal Devon and Exeter NHS Trust

Exeter, , United Kingdom

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Glasgow and Clyde NHS Trust

Glasgow, , United Kingdom

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The Royal Surrey County Hospital NHS Foundation Trust

Guildford, , United Kingdom

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Ipswich Hospital NHS Trust

Ipswich, , United Kingdom

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status

University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

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Royal Marsden NHS Foundation Trust

London, , United Kingdom

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Imperial College Healthcare NHS Trust

London, , United Kingdom

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Barts Health NHS Trust

London, , United Kingdom

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Guys and St Thomas' NHS Foundation Trust

London, , United Kingdom

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University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Maidstone and Tunbridge Wells NHS Trust

Maidstone, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

South Tees Hospitals NHS Trust

Middlesbrough, , United Kingdom

Site Status

Velindre NHS Trust

Nantgarw, , United Kingdom

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Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, , United Kingdom

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Norfolk and Norwich University Hospitals NHS Trust

Norwich, , United Kingdom

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Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

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Portsmouth Hospitals NHS Trust

Portsmouth, , United Kingdom

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Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

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Southend University Hospitals NHS Trust

Southend, , United Kingdom

Site Status

East and North Herts

Stevenage, , United Kingdom

Site Status

Royal Wolverhampton NHS Trust

Wolverhampton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40543520 (View on PubMed)

Related Links

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http://www.ctc.ucl.ac.uk/

Cancer Research UK \& UCL Cancer Trials Centre website

Other Identifiers

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2011-000144-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Cancer Research UK

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ISRCTN

Identifier Type: REGISTRY

Identifier Source: secondary_id

UCL/10/0299

Identifier Type: -

Identifier Source: org_study_id

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