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

Sponsor

University College, London (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01398085

Collaborator

Cancer Research UK (Other)

504

Enrollment

Locations

Arms

226

Duration (Months)

15.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Thyroid Cancer	Radiation: I131 1.1 GBq	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

504 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2012

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2031

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Phase III: Mortality (cause and date of death) [From randomisation until death]
Cause and date of death
Phase III: Occurrence of loco-regional recurrence or metastatic disease [After follow up is complete (estimated year 8-9 of trial)]
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.
Phase III: 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)]
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.
Phase III: Health-related quality of life [After follow up is complete (estimated year 8-9 of trial)]
Quality of Life
Phase III: Adverse events for all patients [After follow up is complete (estimated year 8-9 of trial)]
Adverse events will be collected for patients in both groups during treatment and the groups compared during analysis.
Phase III: Further neck surgery [After follow up is complete (estimated year 8-9 of trial)]
The number of further neck surgeries will be collected for patients in both groups during follow up and the groups compared during analysis.
Phase III: Further RAI ablations [After follow up is complete (estimated year 8-9 of trial)]
Further RAI ablation and the reasons for this
Phase III: Cost-effectiveness [After follow up is complete (estimated year 8-9 of trial)]
Costs of treatment for both groups will be collected for duration of trial to see if there is a difference between the two.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

University College, London
Cancer Research UK

Investigators

Principal Investigator: Ujjal Mallick, MBBS, Master of Surgery, FRCR, Newcastle-upon-Tyne Hospitals NHS Foundation Trust
Study Director: Jonathan Ledermann, University College London (Joint UCLH & UCL Biomedical Research Unit)