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

Study Overview
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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.

Official Title
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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]

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: recombinant thyroid-stimulating hormone
* Radiation: Radiodine ablation without rhTSH


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.1Gbq with rhTSH<br>Patients receive 1.1GBq dose of radioactive iodine and rhTSH | Biological: recombinant thyroid-stimulating hormone<br>* Recombinant thyroid stimulating hormone (rhTSH) should be given at a dose of 0.9mg by intramuscular injection on two consecutive days before ablation.<br>|
| Experimental: 3.2 GBq with rhTSH<br>Patients receive 3.2GBq dose of radioactive idodine and rhTSH | Biological: recombinant thyroid-stimulating hormone<br>* Recombinant thyroid stimulating hormone (rhTSH) should be given at a dose of 0.9mg by intramuscular injection on two consecutive days before ablation.<br>|
| Experimental: 1.1GBq without rhTSH<br>Patients only receive 1.1GBq dose of radioactive iodine and no rhTSH | Radiation: Radiodine ablation without rhTSH<br>* Patients in this group do not receive rhTSH pre ablation.<br>|
| Experimental: 3.2GBq without rhTSH<br>Patients only receive 3.2GBq dose of radioactive iodine and no rhTSH | Radiation: Radiodine ablation without rhTSH<br>* Patients in this group do not receive rhTSH pre ablation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Locoregional recurrence |  | During and post treatment | 
| 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 | 
| Survival |  | 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. | Baseline to 5 years after last patient is randomised | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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