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

University College London (UCL)

Status and phase: Active, not recruiting; Phase 3

Conditions: Head and Neck Cancer

Treatments: Radiation: Radiodine ablation without rhTSH; Biological: recombinant thyroid-stimulating hormone

Study type: Interventional

Funder types: Other

Identifiers

NCT00415233

CRUK-HILO-BRD/05/83 (Other Grant/Funding Number)

ISRCTN56078540 (Registry Identifier)

2005-003687-37 (EudraCT Number)

EU-20665

UCL/05/83

CTA-20363/0217/001/0001 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 438 patients

Sex: All

Ages: 16 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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438 participants in 4 patient groups

1.1Gbq with rhTSH

Experimental group

Description:

Patients receive 1.1GBq dose of radioactive iodine and rhTSH

Treatment:

Biological: recombinant thyroid-stimulating hormone

3.2 GBq with rhTSH

Experimental group

Description:

Patients receive 3.2GBq dose of radioactive idodine and rhTSH

Treatment:

Biological: recombinant thyroid-stimulating hormone

1.1GBq without rhTSH

Experimental group

Description:

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

Treatment:

Radiation: Radiodine ablation without rhTSH

3.2GBq without rhTSH

Experimental group

Description:

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

Treatment:

Radiation: Radiodine ablation without rhTSH