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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

438 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-30

Study Completion Date

2025-07-31

Brief Summary

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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

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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

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Head and Neck Cancer

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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1.1Gbq with rhTSH

Patients receive 1.1GBq dose of radioactive iodine and rhTSH

Group Type EXPERIMENTAL

recombinant thyroid-stimulating hormone

Intervention Type BIOLOGICAL

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

3.2 GBq with rhTSH

Patients receive 3.2GBq dose of radioactive idodine and rhTSH

Group Type EXPERIMENTAL

recombinant thyroid-stimulating hormone

Intervention Type BIOLOGICAL

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

1.1GBq without rhTSH

Patients only receive 1.1GBq dose of radioactive iodine and no rhTSH

Group Type EXPERIMENTAL

Radiodine ablation without rhTSH

Intervention Type RADIATION

Patients in this group do not receive rhTSH pre ablation.

3.2GBq without rhTSH

Patients only receive 3.2GBq dose of radioactive iodine and no rhTSH

Group Type EXPERIMENTAL

Radiodine ablation without rhTSH

Intervention Type RADIATION

Patients in this group do not receive rhTSH pre ablation.

Interventions

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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.

Intervention Type BIOLOGICAL

Radiodine ablation without rhTSH

Patients in this group do not receive rhTSH pre ablation.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

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)

Minimum Eligible Age

16 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ujjal K. Mallick, MD

Role: STUDY_CHAIR

Newcastle-upon-Tyne Hospitals NHS Trust

Locations

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Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

Site Status

Castle Hill Hospital

Cottingham, England, United Kingdom

Site Status

Derbyshire Royal Infirmary

Derby, England, United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, England, United Kingdom

Site Status

St. Luke's Cancer Centre at Royal Surrey County Hospital

Guildford, England, United Kingdom

Site Status

Ipswich Hospital

Ipswich, England, United Kingdom

Site Status

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

Guy's Hospital

London, England, United Kingdom

Site Status

Royal Marsden - London

London, England, United Kingdom

Site Status

Maidstone Hospital

Maidstone, England, United Kingdom

Site Status

Christie Hospital

Manchester, England, United Kingdom

Site Status

James Cook University Hospital

Middlesbrough, England, United Kingdom

Site Status

Newcastle Upon Tyne Hospitals NHS Trust

Newcastle upon Tyne, England, United Kingdom

Site Status

Northampton General Hospital

Northampton, England, United Kingdom

Site Status

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Site Status

Norfolk and Norwich University Hospital

Norwich, England, United Kingdom

Site Status

Dorset Cancer Centre

Poole Dorset, England, United Kingdom

Site Status

Cancer Research Centre at Weston Park Hospital

Sheffield, England, United Kingdom

Site Status

University Hospital of North Staffordshire

Stoke-on-Trent, England, United Kingdom

Site Status

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, United Kingdom

Site Status

Glan Clwyd Hospital

Rhyl, Wales, United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type RESULT

PMID: 22551128 (View on PubMed)

Dehbi 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.

Reference Type DERIVED

PMID: 30501974 (View on PubMed)