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

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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

July 6, 2011
July 20, 2011
October 24, 2018
May 2012
November 2020   (Final data collection date for primary outcome measure)
  • 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
  • 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
  • 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
  • Phase III: 5-year disease-free survival (residual and recurrent) [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
Complete list of historical versions of study NCT01398085 on ClinicalTrials.gov Archive Site
  • Phase III: Mortality (cause and date of death) [ Time Frame: From randomisation until death ]
    Cause and date of death
  • 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.
  • 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.
  • Phase III: Health-related quality of life [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
    Quality of Life
  • 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.
  • 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.
  • 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
  • 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.
  • Phase III: Cause Specific mortality [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
  • Phase III: Loco-regional recurrence [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
  • Phase III: Distant metastases [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
  • Phase III: Quality of Life [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
  • Phase III: Adverse events [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
  • Phase III: Incidence of second primary tumours [ Time Frame: After follow up is complete (estimated year 8-9 of trial) ]
Not Provided
Not Provided
 
IoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients
Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients
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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Thyroid Cancer
Radiation: I131 1.1 GBq
Radio-iodine
Other Name: Sodium iodide capsule
  • Active Comparator: Radioactive iodine (RAI) ablation Arm
    Patients will be randomised to receive Radioactive iodine (RAI) ablation I131 1.1 GBq
    Intervention: Radiation: I131 1.1 GBq
  • No Intervention: No Radioactive iodine (No-RAI) ablation
    Patients will be randomised to receive No Radioactive iodine (No-RAI) ablation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
560
570
January 2021
November 2020   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
16 Years and older   (Child, Adult, Older Adult)
No
Contact: Ihtisham Malik 020 7679 9281 ctc.ion@ucl.ac.uk
Contact: Sharon Forsyth 020 7679 9264 ctc.ion@ucl.ac.uk
United Kingdom
 
 
NCT01398085
UCL/10/0299
2011-000144-21 ( EudraCT Number )
Cancer Research UK ( Other Grant/Funding Number: CRUK/11/010 )
ISRCTN ( Registry Identifier: ISRCTN80416929 )
No
Not Provided
Not Provided
University College, London
University College, London
Cancer Research UK
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)
University College, London
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP