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

University College London (UCL)

Status and phase

Active, not recruiting

Phase 3

Phase 2

Conditions

Thyroid Cancer

Treatments

Radiation: I131 1.1 GBq

Study type

Interventional

Funder types

Other

Identifiers

NCT01398085

2011-000144-21 (EudraCT Number)

ISRCTN (Registry Identifier)

Cancer Research UK (Other Grant/Funding Number)

UCL/10/0299

Details and patient eligibility

About

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.

Full 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.

Enrollment

504 patients

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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