Condition category
Cancer
Date applied
11/01/2011
Date assigned
03/03/2011
Last edited
19/09/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Miss Dymphna Lee

ORCID ID

Contact details

Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
+44 (0)20 7679 9392
ion@ctc.ucl.ac.uk

Additional identifiers

EudraCT number

2011-000144-21

ClinicalTrials.gov number

NCT01398085

Protocol/serial number

UCL/10/0299

Study information

Scientific title

Randomised trial comparing total thyroidectomy, thyriod stimulating hormone (TSH) suppression and radioactive iodine ablation with total thyroidectomy and TSH suppression, in low-risk patients with thyroid cancer

Acronym

ION

Study hypothesis

Phase II:
To determine if recruitment into a phase III trial is feasible, with a target of 10 patients per month during a minimum period of 6 months (evaluated within months 7 - 18 of the trial).

Phase III:
To determine whether the 5-year recurrence-free survival rate among patients who do not have routine radioactive iodine (RAI) ablation is non-inferior to those that do.

As of 06/06/2012, the following changes have been made to the trial.
Anticipated start date has been updated from 02/05/2011 to 16/05/2012.
Anticipated end date has been updated from 05/05/2015 to 16/05/2021 (includes recruitment and follow up phase).
Target number of participants has been increased from 550 to 570.

Ethics approval

Added as of 06/06/2012
North East - Newcastle and Tyneside REC approved on 15/09/2011 (ref: 11/NE/0228)

Birmingham Research Ethics Committee (REC) approval pending as of 12/01/2011

Study design

Randomised non-blind non-inferiority phase II/III multicentre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Differentiated thyroid cancer

Intervention

Following surgery, eligible patients will be approached for consent. Those who agree will be randomised to one of the following groups:
1. Radioactive iodine (RAI) ablation arm (1.1 GBq), or
2. No radioactive iodine (NO-RAI) ablation arm

Total duration of treatment will be from randomisation to last scan (8 - 9 months), and follow-up will be for 5 years.

Chief investigator contact details:
Dr Ujjal Mallick
Freeman Road
High Heaton
Newcastle
NE7 7DN

Intervention type

Other

Phase

Phase II/III

Drug names

Primary outcome measures

1. Phase II: monthly patient accrual rates, evaluated 7 - 18 months after the start. There will then be a decision on whether to proceed to phase III or not
2. Phase III: 5-year recurrence-free survival, evaluated after the last patient has their last follow-up or sooner depending on the data

Secondary outcome measures

Current secondary outcome measure (s) as of 06/06/2012:
Phase III only (evaluated by the statistician at the final analysis at the end of the study):
1. Quality of life (E5-QD, QLQ-C30, H&N35)
2. Adverse events (Common Toxicity Criteria for Adverse Events [CTCAE])
3. Thyroid cancer mortality
4. Loco-regional recurrence
5. Distant metastases
6. Incidence of second primary tumours

Analysis will depend on recruitment but if the trial goes to phase III we expect all patients to be recruited in 3 - 4 years so last visit and analysis will be 8-9 years after the start.

Previous secondary outcome measure (s):
Phase III only (evaluated by the statistician at the final analysis at the end of the study):
1. Quality of life (E5-QD and SF-36)
2. Adverse events (Common Toxicity Criteria for Adverse Events [CTCAE])
3. Thyroid cancer mortality
4. Loco-regional recurrence
5. Distant metastases
6. Incidence of second primary tumours

Analysis will depend on recruitment but if the trial goes to phase III we expect all patients to be recruited in 3 - 4 years so last visit and analysis will be 8-9 years after the start.

Overall trial start date

16/05/2012

Overall trial end date

16/05/2021

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 06/06/2012
1. R0 total thyroidectomy (in 1 or 2 stages, no residual disease present)
2. Negative pregnancy test in females of child bearing potential
3. Aged 16 years or over
4. WHO performance status 0 – 2, self caring
5. Histological confirmation of differentiated thyroid carcinoma
6. Papillary thyroid cancer:
6.1 Non agressive histological features (small foci of agressive histology allowed)
6.2 pT1b, 1-2cm intrathyroidal
6.3 pT2, 2-4cm intrathyroidal
6.4 pT3 intrathyroidal only
6.5 Multifocal carcinoma
6.6 pN0
6.7 pN1a
6.8 pNX
7. Follicular thyroid cancer/Hürthle cell cancer (minimally invasive with capsular invasion only
7.1 pT1b (1-2cm) pT2 (2-4cm) intrathyroidal

Previous inclusion criteria
1. Negative pregnancy test in females of child bearing potential
2. Aged 16 years or over, either sex
3. World Health Organization (WHO) performance status 0 – 2
4. R0 total thyroidectomy (in 1 or 2 stages, no residual disease present)
5. Histological confirmation of differentiated thyroid carcinoma
6. Papillary thyroid cancer:
6.1. Non aggressive histological features (small foci allowed)
6.2. T1b, 1 - 2 cm, intrathyroidal
6.3. T2, 2 - 4 cm, intrathyroidal
6.4. T3, intrathyroidal
6.5. No vascular invasion
6.6. Multifocal microcarcinoma
6.7. N0
6.8. N1a
6.9. NX
7. Follicular thyroid cancer/Hürthle cell cancer:
7.1. Minimally invasive (capsular invasion only)
7.2. Tumours 2 cm or less
7.3. N0
7.4. N1a
7.5. NX

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

570

Participant exclusion criteria

Current exclusion criteria as of 06/06/2012
1. Papillary and Follicular carcinoma which is unifocal and <1cm in size
2. Encapsulated Follicular Variant of Papillary Thyroid Cancer (EFVPTC) that is:
2.1 non-invasive
2.2 angio-invasive
3. Anaplastic or medullary carcinoma
4. R1 thyroidectomy
5. Patients with:
5.1 pN1b
5.2 M1
6. Aggressive Papillary thyroid cancer with the following features:
6.1 Angio-invasive
6.2 Widely invasive
6.3 Poorly differentiated
6.4 Anaplastic differentiation
6.5 Tall cell
6.6 Columnar cell
6.7 Diffuse sclerosing variants
7. Follicular thyroid cancer/Hürthle cell cancer with the following features:
7.1 Angio-invasive
7.2 Widely invasive
7.3 Poorly differentiated
7.4 Tumours greater than 4cm
8. Incomplete resection/lobectomy
9. Macroscopic and microscopic tumour invasion of locoregional tissues or structures
10. Women who are lactating
11. Patients who have had CT performed with iv contrast less than 3 months before ablation
12. Previous treatment for thyroid cancer (except surgery)
13. 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
14. Dysphagia
15. Oesophageal stricture
16. Active gastritis
17. Gastric erosions
18. Peptic ulcer
19. Suspected reduced gastrointestinal motility
20. Severe co-morbid condition/s that would prevent ablation including:
20.1 Unstable angina
20.2 Recent myocardial infarction or cerebrovascular accident (CVA)
20.3 Severe labile hypertension
21. Any patient who cannot comply with radiation protection including:
21.1 patients with learning difficulties
21.2 patients with dementia
21.3 patients with a tracheostomy that require nursing care
21.4 patients requiring frequent nursing/ medical supervision

Previous exclusion criteria
1. Pregnant women or women who are breastfeeding
2. Patients who have computed tomography (CT) performed with intravenous (iv) contrast less than 3 months before ablation
3. Previous treatment for thyroid cancer (not including surgery)
4. Incomplete resection/lobectomy
5. Local or distant metastases at diagnosis
6. Macroscopic and microscopic tumour invasion of locoregional tissues or structures
7. Anaplastic or medullary carcinoma
8. Patients with:
8.1. N1b
8.2. M1
9. Previous malignancies with limited life expectancy likely to interfere with the patient's ability to be able to comply with treatment and/or follow-up
10. Severe co-morbid condition/s that would prevent ablation including:
10.1. Unstable angina
10.2. Recent myocardial infarction or cerebrovascular accident (CVA)
10.3. Severe labile hypertension
10.4. Any patient who cannot comply with radiation protection including:
10.4.1. Patients with learning difficulties
10.4.2. Patients with dementia
10.4.3. Patients with a tracheotomy that require nursing care
10.4.4. Patients requiring frequent nursing/ medical supervision
11. Papillary thyroid cancer that is:
11.1. Widely invasive
11.2. Poorly differentiated
11.3. Tall cell
11.4. Columnar cell
11.5. Diffuse sclerosing variants
12. Follicular thyroid cancer/Hürthle cell cancer that is:
12.1. Widely invasive
12.2. Poorly differentiated
12.3. Tumours greater than 2 cm
12.4. Diffuse sclerosing variants

Recruitment start date

16/05/2012

Recruitment end date

16/05/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK & UCL Cancer Trials Centre
London
W1T 4TJ
United Kingdom

Sponsor information

Organisation

University College London (UCL) (UK)

Sponsor details

1st Floor Maple House
149 Tottenham Court Road
London
W1T7DN
United Kingdom

Sponsor type

University/education

Website

http://www.ucl.ac.uk/joint-rd-unit/

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes