High Dose vs Low Dose I 131 +/- rhTSH for Differentiated Thyroid Cancer

Head and Neck Cancer Clinical Trial

— HiLo  

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]

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00415233
• Other study ID #: UCL/05/83
• Secondary ID: CRUK-HILO-BRD/05
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 2006
• Est. completion date: July 2025

Study information

• Verified date: November 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 438
• Est. completion date: July 2025
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Head and Neck Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Biological:
• recombinant thyroid-stimulating hormone
Recombinant thyroid stimulating hormone (rhTSH) should be given at a dose of 0.9mg by intramuscular injection on two consecutive days before ablation.

Radiation:
• Radiodine ablation without rhTSH
Patients in this group do not receive rhTSH pre ablation.

Locations

Country	Name	City	State
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Castle Hill Hospital	Cottingham	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England
United Kingdom	Northampton General Hospital	Northampton	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Norfolk and Norwich University Hospital	Norwich	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Glan Clwyd Hospital	Rhyl	Wales
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	University Hospital of North Staffordshire	Stoke-On-Trent	England

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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, B — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6-9 months
Secondary	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	Baseline to 3 months
Secondary	Locoregional recurrence		During and post treatment
Secondary	Distant metastases	After the 5 year follow up period, patients will be follwed at hospital according to routine practice.	Baseline to 5 years after randomisation of final patient
Secondary	Survival		Until patient death
Secondary	Incidence of second primary malignancy	After the 5 year follow up period, patients will be follwed at hospital according to routine practice.	Baseline to 5 years after last patient is randomised