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.

Study Type: Interventional

Study Design: Treatment, Randomized

Study Primary Completion Date: November 2009

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.

Intervention(s) in this Clinical Trial

• Drug: iodine I 131
• Drug: liothyronine sodium
• Drug: recombinant thyroid-stimulating hormone
• Drug: thyroxine
• Procedure: adjuvant therapy
• Procedure: quality-of-life assessment

Primary Measures

• Proportion of patients with successful remnant ablation at 6-8 months
  • Safety Issue?: No
• Relative risk of having a successful remnant ablation
  • Safety Issue?: No

Secondary Measures

• Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months
  • Safety Issue?: No
• Locoregional recurrence
  • Safety Issue?: No
• Distant metastases
  • Safety Issue?: No
• Survival
  • Safety Issue?: No
• Incidence of second primary malignancy
  • Safety Issue?: No

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Cancer Research UK

Overall Clinical Trial Officials and Contacts

Ujjal K. Mallick, MD Study Chair Newcastle-upon-Tyne Hospitals NHS Trust  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00415233

Study ID Number: CDR0000522490

ClinicalTrials.gov Identifier: NCT00415233

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database