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

Thyroid Cancer Clinical Trial

— IoN  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01398085
• Other study ID #: UCL/10/0299
• Secondary ID: 2011-000144-21Ca
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: May 2012
• Est. completion date: March 2031

Study information

• Verified date: May 2024
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 504
• Est. completion date: March 2031
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Radiation:
• I131 1.1 GBq
Radio-iodine

Locations

Country	Name	City	State
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton
United Kingdom	University Hospital Bristol NHS Foundation Trust	Bristol
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury
United Kingdom	Mid Essex Hospitals Services NHS Trust	Chelmsford
United Kingdom	Gloucestershire Hospitals NHS Trust	Cheltenham
United Kingdom	Royal Derby hospital NHS foundation trust	Derby
United Kingdom	NHS Lothian	Edinburgh
United Kingdom	Royal Devon and Exeter NHS Trust	Exeter
United Kingdom	Glasgow and Clyde NHS Trust	Glasgow
United Kingdom	The Royal Surrey County Hospital NHS Foundation Trust	Guildford
United Kingdom	Ipswich Hospital NHS Trust	Ipswich
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Guys and St Thomas' NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Marsden NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	Maidstone and Tunbridge Wells NHS Trust	Maidstone
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	South Tees Hospitals NHS Trust	Middlesbrough
United Kingdom	Velindre NHS Trust	Nantgarw
United Kingdom	Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle
United Kingdom	Norfolk and Norwich University Hospitals NHS Trust	Norwich
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Portsmouth Hospitals NHS Trust	Portsmouth
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	Southend University Hospitals NHS Trust	Southend
United Kingdom	East and North Herts	Stevenage
United Kingdom	Royal Wolverhampton NHS Trust	Wolverhampton

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Phase III: Mortality (cause and date of death)	Cause and date of death	From randomisation until death
Secondary	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)
Secondary	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)
Secondary	Phase III: Health-related quality of life	Quality of Life	After follow up is complete (estimated year 8-9 of trial)
Secondary	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)
Secondary	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)
Secondary	Phase III: Further RAI ablations	Further RAI ablation and the reasons for this	After follow up is complete (estimated year 8-9 of trial)
Secondary	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)

External Links

•   Cancer Research UK & UCL Cancer Trials Centre website