Head and Neck CancerPhase 3HiLoNCT00415233
High Dose vs Low Dose I 131 +/- rhTSH for Differentiated Thyroid Cancer
A Phase 3 study testing recombinant thyroid-stimulating hormone and Radiodine ablation without rhTSH in people with Head and Neck Cancer, run by University College, London at 25 sites in United Kingdom.
Trial summary
RATIONALE: Radioactive iodine uses radiation to kill tumor cells. Giving iodine I 131 with or without thyroid-stimulating hormone after surgery may kill any tumor cells that remain after surgery. Read more about this study
- Who is it for?
- Ages 16 to 80 years
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- recombinant thyroid-stimulating hormone and Radiodine ablation without rhTSH
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 438 participants
- Where
- 25 sitesUnited Kingdom
- Study dates
- Nov 2006to Jul 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed differentiated thyroid cancer
- T1-T3, Nx, N0, N1, M0 disease
- Has undergone one- or two-stage total thyroidectomy with or without lymph node dissection
- All known tumor resected (R0)
- Requires radioiodine remnant ablation
- Does not require mandatory recombinant thyroid-stimulating hormone
- No Hurthle cell carcinoma or aggressive variants, including any of the following:
- Tall cell, insular, poorly differentiated disease with diffuse sclerosing
- Anaplastic or medullary carcinoma
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- No severe comorbid conditions including, but not limited to, any of the following:
- Unstable angina
- Recent heart attack or stroke
- Severe labile hypertension
- Dementia
- Concurrent dialysis
- Tracheostomy needing care
- Learning difficulties
- Inability to comply with radiation protection issues
- Requirement for frequent nursing or medical supervision that puts staff at risk for unacceptable radiation exposure
- No other cancers except basal cell skin cancer or carcinoma in situ of the cervix
- Not pregnant or nursing
- Negative pregnancy test
- Fertile female patients must use effective contraception during and for 6 months after radioiodine remnant ablation
- Fertile male patients must use effective contraception during and for 4 months after radioiodine remnant ablation
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 3 months since prior contrast CT scan
- No prior iodine I 131 or iodine I 123 pre-ablation scan
- No prior treatment for thyroid cancer (except surgery)
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United Kingdom25 sites
Sussex Cancer Centre at Royal Sussex County Hospital
Brighton, England, BN2 5BE
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Kent and Canterbury Hospital
Canterbury, England, CT1 3NG
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, CF14 2TL
Castle Hill Hospital
Cottingham, England, HU16 5JQ
Derbyshire Royal Infirmary
Derby, England, DE1 2QY
Royal Devon and Exeter Hospital
Exeter, England, EX2 5DW
Gloucestershire Royal Hospital
Gloucester, England, GL1 3NN
St. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, GU2 7XX
Ipswich Hospital
Ipswich, England, IP4 5PD
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Leicester Royal Infirmary
Leicester, England, LE1 5WW
Guy's Hospital
London, England, SE1 9RT
Royal Marsden - London
London, England, SW3 6JJ
Maidstone Hospital
Maidstone, England, ME16 9QQ
Christie Hospital
Manchester, England, M20 4BX
James Cook University Hospital
Middlesbrough, England, TS4 3BW
Newcastle Upon Tyne Hospitals NHS Trust
Newcastle upon Tyne, England, NE4 6BE
Northampton General Hospital
Northampton, England, NN1 5BD
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, HA6 2RN
Norfolk and Norwich University Hospital
Norwich, England, NR4 7UY
Dorset Cancer Centre
Poole Dorset, England, BH15 2JB
Glan Clwyd Hospital
Rhyl, Wales, LL 18 5UJ
Cancer Research Centre at Weston Park Hospital
Sheffield, England, S10 2SJ
University Hospital of North Staffordshire
Stoke-on-Trent, England, ST4 7LN
About this study
Official title: Multicentre Randomised Trial of High Dose Versus Low Dose Radioiodine, With or Without Recombinant Human Thyroid Stimulating Hormone, for Remnant Ablation Following Surgery for Differentiated Thyroid Cancer [HILO]
RATIONALE: Radioactive iodine uses radiation to kill tumor cells. Giving iodine I 131 with or without thyroid-stimulating hormone after surgery may kill any tumor cells that remain after surgery. It is not yet known which dose of iodine I 131 is more effective when given with or without thyroid-stimulating hormone in treating thyroid cancer.
PURPOSE: This randomized phase III trial is studying two different doses of iodine I 131 to compare how well they work when given with or without thyroid-stimulating hormone in treating patients who have undergone surgery for thyroid cancer.
Read the detailed description
OBJECTIVES:
Primary
- Compare the percentage of successful remnant ablation at 6-8 months after administration of high- vs low-dose iodine I 131 with vs without recombinant thyroid-stimulating hormone in patients who have undergone total thyroidectomy for differentiated thyroid cancer.
Secondary
- Compare quality of life in patients treated with these regimens.
- Compare locoregional recurrence in patients treated with these regimens.
- Compare distant metastases, survival, and incidence of second primary malignancies in patients treated with these regimens.
OUTLINE: This is a multicenter, factorial, randomized study. Patients are stratified according to treatment center and disease stage (I vs II vs III vs IVA). Patients are randomized to 1 of 4 treatment arms.
Patients receive thyroid hormone replacement therapy (THRT)* with thyroxine (T4)** or liothyronine sodium (T3). Patients randomized to arm III or IV discontinue THRT 4 weeks (for patients receiving T4) or 2 weeks (for patients receiving T3) prior to remnant ablation.
NOTE: *Some treatment centers may chose to avoid starting THRT in patients randomized to arm III or IV.
NOTE: **Patients receiving T4 may be switched to T3 for 2 more weeks before discontinuing THRT.
- Arm I: Patients receive recombinant thyroid-stimulating hormone (rTSH) intramuscularly on days 1 and 2 and undergo remnant ablation with low-dose iodine I 131 on day 3.
- Arm II: Patients receive rTSH as in arm I and undergo remnant ablation with high-dose iodine I 131 on day 3.
- Arm III: Patients undergo remnant ablation with low-dose iodine I 131 as in arm I.
- Arm IV: Patients undergo remnant ablation with high-dose iodine I 131 as in arm II.
Quality of life is assessed at baseline, day 3 before remnant ablation, and at 3 months.
After completion of study therapy, patients are followed at 3 months, between 6-8 months, and then annually thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 468 patients will be accrued for this study.
- Conditions
- Head and Neck Cancer
- Being tested
- recombinant thyroid-stimulating hormone, Radiodine ablation without rhTSH
- Keywords
- stage I follicular thyroid cancer, stage I papillary thyroid cancer, stage II follicular thyroid cancer, stage II papillary thyroid cancer, stage III follicular thyroid cancer, stage III papillary thyroid cancer, stage IV follicular thyroid cancer, stage IV papillary thyroid cancer
- Medical subject headings
- Head and Neck Neoplasms, Adenocarcinoma, Follicular, Thyroid Cancer, Papillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant thyroid-stimulating hormoneBiological
Recombinant thyroid stimulating hormone (rhTSH) should be given at a dose of 0.9mg by intramuscular injection on two consecutive days before ablation.
Radiodine ablation without rhTSHRadiation
Patients in this group do not receive rhTSH pre ablation.
| Study group | Role | What they receive |
|---|---|---|
| 1.1Gbq with rhTSH | Experimental | Patients receive 1.1GBq dose of radioactive iodine and rhTSH Receives: Biological: recombinant thyroid-stimulating hormone |
| 3.2 GBq with rhTSH | Experimental | Patients receive 3.2GBq dose of radioactive idodine and rhTSH Receives: Biological: recombinant thyroid-stimulating hormone |
| 1.1GBq without rhTSH | Experimental | Patients only receive 1.1GBq dose of radioactive iodine and no rhTSH Receives: Radiation: Radiodine ablation without rhTSH |
| 3.2GBq without rhTSH | Experimental | Patients only receive 3.2GBq dose of radioactive iodine and no rhTSH Receives: Radiation: Radiodine ablation without rhTSH |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with successful remnant ablation at 6-9 months
The percentage of patients who have a successful remnant ablation at 6-9 months after radioiodine administration.
Measured: 6-9 months
Secondary outcomes (5)
Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months
Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months
Measured: Baseline to 3 months
Locoregional recurrence
Measured: During and post treatment
Distant metastases
After the 5 year follow up period, patients will be follwed at hospital according to routine practice.
Measured: Baseline to 5 years after randomisation of final patient
Survival
Measured: Until patient death
Incidence of second primary malignancy
After the 5 year follow up period, patients will be follwed at hospital according to routine practice.
Measured: Baseline to 5 years after last patient is randomised
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2006 (estimated)
- Study startNov 2006
- Primary completionJun 2011
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 438 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ujjal K. Mallick, MD, Study chair, Newcastle-upon-Tyne Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00415233
- Sponsor's protocol ID
- UCL/05/83
- Other IDs
- CRUK-HILO-BRD/05/83, ISRCTN56078540, EU-20665, CTA-20363/0217/001/0001, 2005-003687-37, 2005
- Acronym
- HiLo
- Status last verified
- Nov 2023
- First submitted
- 20 Dec 2006
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012 May 3;366(18):1674-85. doi: 10.1056/NEJMoa1109589.
PubMed 22551128Dehbi HM, Mallick U, Wadsley J, Newbold K, Harmer C, Hackshaw A. Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Jan;7(1):44-51. doi: 10.1016/S2213-8587(18)30306-1. Epub 2018 Nov 27.
PubMed 30501974
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre Randomised Trial of High Dose Versus Low Dose Radioiodine, With or Without Recombinant Human Thyroid Stimulating Hormone, for Remnant Ablation Following Surgery for Differentiated Thyroid Cancer [HILO]
- ClinicalTrials.gov ID
- NCT00415233
- Acronym / sponsor ID
- HiLo / UCL/05/83
- Conditions
- Head and Neck Cancer
- Keywords
- stage I follicular thyroid cancer, stage I papillary thyroid cancer, stage II follicular thyroid cancer, stage II papillary thyroid cancer, stage III follicular thyroid cancer, stage III papillary thyroid cancer, stage IV follicular thyroid cancer, stage IV papillary thyroid cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 438 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Nov 2006 (actual)
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jul 2025 (estimated)
- First posted
- 22 Dec 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Radioactive iodine uses radiation to kill tumor cells. Giving iodine I 131 with or without thyroid-stimulating hormone after surgery may kill any tumor cells that remain after surgery. It is not yet known which dose of iodine I 131 is more effective when given with or without thyroid-stimulating hormone in treating thyroid cancer.
PURPOSE: This randomized phase III trial is studying two different doses of iodine I 131 to compare how well they work when given with or without thyroid-stimulating hormone in treating patients who have undergone surgery for thyroid cancer.
Detailed description
OBJECTIVES:
Primary
- Compare the percentage of successful remnant ablation at 6-8 months after administration of high- vs low-dose iodine I 131 with vs without recombinant thyroid-stimulating hormone in patients who have undergone total thyroidectomy for differentiated thyroid cancer.
Secondary
- Compare quality of life in patients treated with these regimens.
- Compare locoregional recurrence in patients treated with these regimens.
- Compare distant metastases, survival, and incidence of second primary malignancies in patients treated with these regimens.
OUTLINE: This is a multicenter, factorial, randomized study. Patients are stratified according to treatment center and disease stage (I vs II vs III vs IVA). Patients are randomized to 1 of 4 treatment arms.
Patients receive thyroid hormone replacement therapy (THRT)* with thyroxine (T4)** or liothyronine sodium (T3). Patients randomized to arm III or IV discontinue THRT 4 weeks (for patients receiving T4) or 2 weeks (for patients receiving T3) prior to remnant ablation.
NOTE: *Some treatment centers may chose to avoid starting THRT in patients randomized to arm III or IV.
NOTE: **Patients receiving T4 may be switched to T3 for 2 more weeks before discontinuing THRT.
- Arm I: Patients receive recombinant thyroid-stimulating hormone (rTSH) intramuscularly on days 1 and 2 and undergo remnant ablation with low-dose iodine I 131 on day 3.
- Arm II: Patients receive rTSH as in arm I and undergo remnant ablation with high-dose iodine I 131 on day 3.
- Arm III: Patients undergo remnant ablation with low-dose iodine I 131 as in arm I.
- Arm IV: Patients undergo remnant ablation with high-dose iodine I 131 as in arm II.
Quality of life is assessed at baseline, day 3 before remnant ablation, and at 3 months.
After completion of study therapy, patients are followed at 3 months, between 6-8 months, and then annually thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 468 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1.1Gbq with rhTSH | Experimental | Biological: recombinant thyroid-stimulating hormonePatients receive 1.1GBq dose of radioactive iodine and rhTSH |
| 3.2 GBq with rhTSH | Experimental | Biological: recombinant thyroid-stimulating hormonePatients receive 3.2GBq dose of radioactive idodine and rhTSH |
| 1.1GBq without rhTSH | Experimental | Radiation: Radiodine ablation without rhTSHPatients only receive 1.1GBq dose of radioactive iodine and no rhTSH |
| 3.2GBq without rhTSH | Experimental | Radiation: Radiodine ablation without rhTSHPatients only receive 3.2GBq dose of radioactive iodine and no rhTSH |
Who may qualify
- Ages
- 16 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant thyroid-stimulating hormoneRecombinant thyroid stimulating hormone (rhTSH) should be given at a dose of 0.9mg by intramuscular injection on two consecutive days before ablation. | Biological | 1.1Gbq with rhTSH, 3.2 GBq with rhTSH |
| Radiodine ablation without rhTSHPatients in this group do not receive rhTSH pre ablation. | Radiation | 1.1GBq without rhTSH, 3.2GBq without rhTSH |
Primary outcome
Proportion of patients with successful remnant ablation at 6-9 months
Time frame: 6-9 months
The percentage of patients who have a successful remnant ablation at 6-9 months after radioiodine administration.
5 secondary outcomes
Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months
Time frame: Baseline to 3 months
Locoregional recurrence
Time frame: During and post treatment
Distant metastases
Time frame: Baseline to 5 years after randomisation of final patient
Survival
Time frame: Until patient death
Incidence of second primary malignancy
Time frame: Baseline to 5 years after last patient is randomised
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Results publication: PubMed 22551128Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012 May 3;366(18):1674-85. doi: 10.1056/NEJMoa1109589.
- Derived from this study: PubMed 30501974Dehbi HM, Mallick U, Wadsley J, Newbold K, Harmer C, Hackshaw A. Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Jan;7(1):44-51. doi: 10.1016/S2213-8587(18)30306-1. Epub 2018 Nov 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ujjal K. Mallick, MD study chair
Newcastle-upon-Tyne Hospitals NHS Trust
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing recombinant thyroid-stimulating hormone and Radiodine ablation without rhTSH in people with Head and Neck Cancer, run by University College, London at 25 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with successful remnant ablation at 6-9 months (time frame: 6-9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00415233, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.