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

Primary Purpose

Thyroid Cancer

Status

Active

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

I131 1.1 GBq

About this trial

This is an interventional treatment trial for Thyroid Cancer focused on measuring Papillary thyroid carcinoma, Follicular thyroid carcinoma, Hurthle cell carcinoma of the thyroid, Iodine Radioisotopes

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Radioactive iodine (RAI) ablation Arm

No Radioactive iodine (No-RAI) ablation

Arm Description

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

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

Outcomes

Primary Outcome Measures

Phase II: monthly patient accrual rates

To determine if recruitment into a phase III trial is feasible

Phase III: Disease-free thyroid specific survival

DFS measured from randomisation until date of recurrence or death from thyroid cancer

Secondary Outcome Measures

Phase III: Mortality (cause and date of death)

Cause and date of death

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.

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.

Phase III: Health-related quality of life

Quality of Life

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.

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.

Phase III: Further RAI ablations

Further RAI ablation and the reasons for this

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.

Full Information

NCT ID

NCT01398085

First Posted

July 6, 2011

Last Updated

June 8, 2023

Sponsor

University College, London

Collaborators

Cancer Research UK

1. Study Identification

Unique Protocol Identification Number

NCT01398085

Brief Title

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

Acronym

IoN

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 2012 (undefined)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

March 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University College, London

Collaborators

Cancer Research UK

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thyroid Cancer

Keywords

Papillary thyroid carcinoma, Follicular thyroid carcinoma, Hurthle cell carcinoma of the thyroid, Iodine Radioisotopes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

504 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Radioactive iodine (RAI) ablation Arm

Arm Type

Active Comparator

Arm Description

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

Arm Title

No Radioactive iodine (No-RAI) ablation

Arm Type

No Intervention

Arm Description

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

Intervention Type

Radiation

Intervention Name(s)

I131 1.1 GBq

Other Intervention Name(s)

Sodium iodide capsule

Intervention Description

Radio-iodine

Primary Outcome Measure Information:

Title

Phase II: monthly patient accrual rates

Description

To determine if recruitment into a phase III trial is feasible

Time Frame

Evaluated within months 7-18 of the trial

Title

Phase III: Disease-free thyroid specific survival

Description

DFS measured from randomisation until date of recurrence or death from thyroid cancer

Time Frame

From randomisation until recurrence or death from thyroid cancer

Secondary Outcome Measure Information:

Title

Phase III: Mortality (cause and date of death)

Description

Cause and date of death

Time Frame

From randomisation until death

Title

Phase III: Occurrence of loco-regional recurrence or metastatic disease

Description

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.

Time Frame