ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01398085
Recruitment Status : Recruiting
First Posted : July 20, 2011
Last Update Posted : October 24, 2018
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
University College, London

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 560 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 2012
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : January 2021


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 Name: Sodium iodide capsule

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



Primary Outcome Measures :
  1. Phase II: monthly patient accrual rates [ Time Frame: Evaluated within months 7-18 of the trial ]
    To determine if recruitment into a phase III trial is feasible

  2. Phase III: Disease-free thyroid specific survival [ Time Frame: 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 :
  1. Phase III: Mortality (cause and date of death) [ Time Frame: From randomisation until death ]
    Cause and date of death

  2. Phase III: Occurrence of loco-regional recurrence or metastatic disease [ Time Frame: 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.

  3. Phase III: Stage of cancer at the time of recurrence, and the ability to treat this successfully [ Time Frame: 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.

  4. Phase III: Health-related quality of life [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
    Quality of Life

  5. Phase III: Adverse events for all patients [ Time Frame: 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.

  6. Phase III: Further neck surgery [ Time Frame: 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.

  7. Phase III: Further RAI ablations [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
    Further RAI ablation and the reasons for this

  8. Phase III: Cost-effectiveness [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 supervisi

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01398085


Contacts
Contact: Ihtisham Malik 020 7679 9281 ctc.ion@ucl.ac.uk
Contact: Sharon Forsyth 020 7679 9264 ctc.ion@ucl.ac.uk

Locations
United Kingdom
University Hospitals Birmingham NHS Foundation Trust Recruiting
Birmingham, United Kingdom
Principal Investigator: Hisham Mehanna         
Brighton and Sussex University Hospitals NHS Trust Recruiting
Brighton, United Kingdom, BN2 5BE
Principal Investigator: Joanna Simpson         
University Hospital Bristol NHS Foundation Trust Recruiting
Bristol, United Kingdom, BS1 3NU
Principal Investigator: Matthew Beasley         
Cambridge University Hospitals NHS Foundation Trust Recruiting
Cambridge, United Kingdom, CB2 0QQ
Principal Investigator: Sarah Jefferies         
East Kent Hospitals University NHS Foundation Trust Recruiting
Canterbury, United Kingdom, CT1 3NG
Principal Investigator: Alistair Balfour         
Mid Essex Hospitals Services NHS Trust Recruiting
Chelmsford, United Kingdom
Principal Investigator: Abdel Hamid         
Gloucestershire Hospitals NHS Trust Recruiting
Cheltenham, United Kingdom
Principal Investigator: Charles Candish         
Royal Derby hospital NHS foundation trust Not yet recruiting
Derby, United Kingdom, DE223NE
Principal Investigator: Rengarajan Vijayan         
NHS Lothian Recruiting
Edinburgh, United Kingdom, EH4 2XU
Principal Investigator: Mark Strachan         
Royal Devon and Exeter NHS Trust Recruiting
Exeter, United Kingdom, EX2 5DW
Principal Investigator: Andy Goodman         
Glasgow and Clyde NHS Trust Recruiting
Glasgow, United Kingdom, G12 0YN
Principal Investigator: Nick Reed         
The Royal Surrey County Hospital NHS Foundation Trust Recruiting
Guildford, United Kingdom, GU1 4JW
Principal Investigator: Stephen Whitaker         
Ipswich Hospital NHS Trust Recruiting
Ipswich, United Kingdom, IP4 5PD
Principal Investigator: Christopher Scrase         
Leeds Teaching Hospitals NHS Trust Recruiting
Leeds, United Kingdom, LS9 7TF
Principal Investigator: Vanessa Gill         
University Hospitals of Leicester NHS Trust Recruiting
Leicester, United Kingdom, LE1 5WW
Principal Investigator: Lesley Speed         
Royal Marsden NHS Foundation Trust Recruiting
London, United Kingdom, SW3 6JJ
Principal Investigator: Chris Nutting         
Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom, W6 8RF
Principal Investigator: Danielle Power         
Barts Health NHS Trust Recruiting
London, United Kingdom
Principal Investigator: Ayesha Siddiqi         
Guys and St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom
Principal Investigator: Fahim Hassan         
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Principal Investigator: Mark Gaze         
Maidstone and Tunbridge Wells NHS Trust Recruiting
Maidstone, United Kingdom, ME16 9QQ
Principal Investigator: Nick Rowell         
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Kate Garcez         
South Tees Hospitals NHS Trust Recruiting
Middlesbrough, United Kingdom, TS4 3BW
Principal Investigator: David Wilkinson         
Velindre NHS Trust Recruiting
Nantgarw, United Kingdom, CF15 7QZ
Principal Investigator: Laura Moss         
Newcastle upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle, United Kingdom, NE7 7DN
Principal Investigator: Peter Truran         
Norfolk and Norwich University Hospitals NHS Trust Recruiting
Norwich, United Kingdom
Principal Investigator: Tom Roques         
Nottingham University Hospitals NHS Trust Recruiting
Nottingham, United Kingdom, NG5 1PB
Principal Investigator: Abigail Pascoe         
Poole Hospital NHS Foundation Trust Withdrawn
Poole, United Kingdom, DT1 2JY
Portsmouth Hospitals NHS Trust Recruiting
Portsmouth, United Kingdom
Principal Investigator: David Boote         
Sheffield Teaching Hospitals NHS Foundation Trust Recruiting
Sheffield, United Kingdom, S10 2SJ
Principal Investigator: Jon Wadsley         
Southend University Hospitals NHS Trust Recruiting
Southend, United Kingdom, SS0 0RY
Principal Investigator: Krishnaswamy Madhavan         
East and North Herts Not yet recruiting
Stevenage, United Kingdom, SG1 4AB
Principal Investigator: George Mochloulis         
Royal Wolverhampton NHS Trust Recruiting
Wolverhampton, United Kingdom
Principal Investigator: Devashish Tripathi         
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)

Additional Information:
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01398085     History of Changes
Other Study ID Numbers: UCL/10/0299
2011-000144-21 ( EudraCT Number )
Cancer Research UK ( Other Grant/Funding Number: CRUK/11/010 )
ISRCTN ( Registry Identifier: ISRCTN80416929 )
First Posted: July 20, 2011    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018

Keywords provided by University College, London:
Papillary thyroid carcinoma
Follicular thyroid carcinoma
Hurthle cell carcinoma of the thyroid
Iodine Radioisotopes

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Iodine
Cadexomer iodine
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs