Clinical trial NCT01398085: IoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients
Official title: Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Thyroid Cancer
Keywords: Papillary thyroid carcinoma
Follicular thyroid carcinoma
Hurthle cell carcinoma of the thyroid
Iodine Radioisotopes
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
First posted: 2011-07-20
Enrollment: 504
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Phase II: monthly patient accrual rates
timeFrame: Evaluated within months 7-18 of the trial
measure: Phase III: Disease-free thyroid specific survival
timeFrame: From randomisation until recurrence or death from thyroid cancer
Secondary outcomes:
measure: Phase III: Mortality (cause and date of death)
timeFrame: From randomisation until death
measure: Phase III: Occurrence of loco-regional recurrence or metastatic disease
timeFrame: After follow up is complete (estimated year 8-9 of trial)
measure: Phase III: Stage of cancer at the time of recurrence, and the ability to treat this successfully
timeFrame: After follow up is complete (estimated year 8-9 of trial)
measure: Phase III: Health-related quality of life
timeFrame: After follow up is complete (estimated year 8-9 of trial)
measure: Phase III: Adverse events for all patients
timeFrame: After follow up is complete (estimated year 8-9 of trial)
measure: Phase III: Further neck surgery
timeFrame: After follow up is complete (estimated year 8-9 of trial)
measure: Phase III: Further RAI ablations
timeFrame: After follow up is complete (estimated year 8-9 of trial)
measure: Phase III: Cost-effectiveness
timeFrame: After follow up is complete (estimated year 8-9 of trial)
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: Bristol
country: United Kingdom
facility: University Hospital Bristol NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust
city: Chelmsford
country: United Kingdom
facility: Mid Essex Hospitals Services NHS Trust
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Hospitals NHS Trust
city: Derby
country: United Kingdom
facility: Royal Derby hospital NHS foundation trust
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Trust
city: Glasgow
country: United Kingdom
facility: Glasgow and Clyde NHS Trust
city: Guildford
country: United Kingdom
facility: The Royal Surrey County Hospital NHS Foundation Trust
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Guys and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Maidstone
country: United Kingdom
facility: Maidstone and Tunbridge Wells NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Trust
city: Nantgarw
country: United Kingdom
facility: Velindre NHS Trust
city: Newcastle
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Southend
country: United Kingdom
facility: Southend University Hospitals NHS Trust
city: Stevenage
country: United Kingdom
facility: East and North Herts
city: Wolverhampton
country: United Kingdom
facility: Royal Wolverhampton NHS Trust
Study officials:
affiliation: Newcastle-upon-Tyne Hospitals NHS Foundation Trust
name: Ujjal Mallick, MBBS, Master of Surgery, FRCR
role: PRINCIPAL_INVESTIGATOR
References: