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

Sponsor

University College, London (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00415233

Collaborator

(none)

438

Enrollment

Locations

Arms

224

Anticipated Duration (Months)

17.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Biological: recombinant thyroid-stimulating hormone Radiation: Radiodine ablation without rhTSH	Phase 3

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

Study Type:

Interventional

Actual Enrollment :

438 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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]

Actual Study Start Date :

Nov 1, 2006

Actual Primary Completion Date :

Jun 1, 2011

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1.1Gbq with rhTSH Patients receive 1.1GBq dose of radioactive iodine and rhTSH	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.
Experimental: 3.2 GBq with rhTSH Patients receive 3.2GBq dose of radioactive idodine and rhTSH	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.
Experimental: 1.1GBq without rhTSH Patients only receive 1.1GBq dose of radioactive iodine and no rhTSH	Radiation: Radiodine ablation without rhTSH Patients in this group do not receive rhTSH pre ablation.
Experimental: 3.2GBq without rhTSH Patients only receive 3.2GBq dose of radioactive iodine and no rhTSH	Radiation: Radiodine ablation without rhTSH Patients in this group do not receive rhTSH pre ablation.

Outcome Measures

Primary Outcome Measures

Proportion of patients with successful remnant ablation at 6-9 months [6-9 months]
The percentage of patients who have a successful remnant ablation at 6-9 months after radioiodine administration.

Secondary Outcome Measures

Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months [Baseline to 3 months]
Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months
Locoregional recurrence [During and post treatment]
Distant metastases [Baseline to 5 years after randomisation of final patient]
After the 5 year follow up period, patients will be follwed at hospital according to routine practice.
Survival [Until patient death]
Incidence of second primary malignancy [Baseline to 5 years after last patient is randomised]
After the 5 year follow up period, patients will be follwed at hospital according to routine practice.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England	United Kingdom	BN2 5BE
2	Addenbrooke's Hospital	Cambridge	England	United Kingdom	CB2 2QQ
3	Kent and Canterbury Hospital	Canterbury	England	United Kingdom	CT1 3NG
4	Castle Hill Hospital	Cottingham	England	United Kingdom	HU16 5JQ
5	Derbyshire Royal Infirmary	Derby	England	United Kingdom	DE1 2QY
6	Royal Devon and Exeter Hospital	Exeter	England	United Kingdom	EX2 5DW
7	Gloucestershire Royal Hospital	Gloucester	England	United Kingdom	GL1 3NN
8	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England	United Kingdom	GU2 7XX
9	Ipswich Hospital	Ipswich	England	United Kingdom	IP4 5PD
10	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
11	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
12	Guy's Hospital	London	England	United Kingdom	SE1 9RT
13	Royal Marsden - London	London	England	United Kingdom	SW3 6JJ
14	Maidstone Hospital	Maidstone	England	United Kingdom	ME16 9QQ
15	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
16	James Cook University Hospital	Middlesbrough	England	United Kingdom	TS4 3BW
17	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England	United Kingdom	NE4 6BE
18	Northampton General Hospital	Northampton	England	United Kingdom	NN1 5BD
19	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England	United Kingdom	HA6 2RN
20	Norfolk and Norwich University Hospital	Norwich	England	United Kingdom	NR4 7UY
21	Dorset Cancer Centre	Poole Dorset	England	United Kingdom	BH15 2JB
22	Cancer Research Centre at Weston Park Hospital	Sheffield	England	United Kingdom	S10 2SJ
23	University Hospital of North Staffordshire	Stoke-On-Trent	England	United Kingdom	ST4 7LN
24	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales	United Kingdom	CF14 2TL
25	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales	United Kingdom	LL 18 5UJ