Iodine I 131 With or Without Thyroid-Stimulating Hormone in Treating Patients Who Have Undergone Surgery for Thyroid Cancer

Condition(s) targeted: Head and Neck Cancer

Intervention: recombinant thyroid-stimulating hormone (Biological); liothyronine sodium (Drug); thyroxine (Drug); adjuvant therapy (Procedure); quality-of-life assessment (Procedure); iodine I 131 (Radiation)

Phase: Phase 3

Status: Recruiting

Sponsored by: Cancer Research UK

Official(s) and/or principal investigator(s):
Ujjal K. Mallick, MD, Study Chair, Affiliation: Newcastle-upon-Tyne Hospitals NHS Trust

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.

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]

Study design: Treatment, Randomized

Primary outcome:

Proportion of patients with successful remnant ablation at 6-8 months

Relative risk of having a successful remnant ablation

Secondary outcome:

Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months

Locoregional recurrence

Distant metastases

Survival

Incidence of second primary malignancy

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.

Minimum age: 16 Years. Maximum age: 80 Years. Gender(s): Both.

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)

Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom; Recruiting
Sarah Jefferies, Phone: 44-1223-245-151

Cancer Research Centre at Weston Park Hospital, Sheffield, England S1O 2SJ, United Kingdom; Recruiting
Jonathan Wadsley, Phone: 44-114-226-5000

Castle Hill Hospital, Cottingham, England HU16 5JQ, United Kingdom; Recruiting
Contact Person, Phone: 44-1482-659-331

Christie Hospital, Manchester, England M20 4BX, United Kingdom; Recruiting
Beng Yap, MD, Phone: 44-845-226-3000

Derbyshire Royal Infirmary, Derby, England DE1 2QY, United Kingdom; Recruiting
Contact Person, Phone: 44-1332-347-141 ext. 2407

Dorset Cancer Centre, Poole Dorset, England BH15 2JB, United Kingdom; Recruiting
Contact Person, Phone: 44-1202-448-263

Gloucestershire Royal Hospital, Gloucester, England GL1 3NN, United Kingdom; Recruiting
Contact Person, Phone: 44-8454-222-222

Guy's Hospital, London, England SE1 9RT, United Kingdom; Recruiting
Sue Clarke, MD, Phone: 44-20-7188-7188

Ipswich Hospital, Ipswich, England IP4 5PD, United Kingdom; Recruiting
Christopher Scrase, MD, Phone: 44-147-370-4177

James Cook University Hospital, Middlesbrough, England TS4 3BW, United Kingdom; Recruiting
Contact Person, Phone: 44-1642-850-850

Kent and Canterbury Hospital, Canterbury, England CT1 3NG, United Kingdom; Recruiting
Contact Person, Phone: 44-1227-766-877

Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom; Recruiting
Contact Person, Phone: 44-113-206-6400

Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom; Recruiting
Contact Person, Phone: 44-116-254-1414

Maidstone Hospital, Maidstone, England ME16 9QQ, United Kingdom; Recruiting
Nick P. Rowell, MD, Phone: 44-1622-225-103, Email: nrowell@koc.mtw-tr.nhs.uk

Mount Vernon Cancer Centre at Mount Vernon Hospital, Northwood, England HA6 2RN, United Kingdom; Recruiting
Catherine Lemon, MD, Phone: 44-1923-826-111

Newcastle Upon Tyne Hospitals NHS Trust, Newcastle-Upon-Tyne, England NE4 6BE, United Kingdom; Recruiting
Ujjal K. Mallick, MD, Phone: 44-191-256-3571

Norfolk and Norwich University Hospital, Norwich, England NR4 7UY, United Kingdom; Recruiting
Tom W. Roques, MD, Phone: 44-603-287-671, Email: tom.roques@nnuh.nhs.uk

Northampton General Hospital NHS Trust, Northampton, England NN1 5BD, United Kingdom; Recruiting
Contact Person, Phone: 44-1604-63-4700

Royal Devon and Exeter Hospital, Exeter, England EX2 5DW, United Kingdom; Recruiting
Andrew Goodman, MD, Phone: 44-1392-411-611

Royal Marsden - London, London, England SW3 6JJ, United Kingdom; Recruiting
Chris Nutting, Phone: 44-20-7808-2586, Email: Chris.Nutting@rmh.nthames.nhs.uk

St. Luke's Cancer Centre at Royal Surrey County Hospital, Guildford, England GU2 7XX, United Kingdom; Recruiting
Stephen Whitaker, MD, Phone: 44-1483-571-122

Sussex Cancer Centre at Royal Sussex County Hospital, Brighton, England BN2 5BE, United Kingdom; Recruiting
Contact Person, Phone: 44-12-7369-6955

University Hospital of North Staffordshire, Stoke-On-Trent, England ST4 7LN, United Kingdom; Recruiting
Contact Person, Phone: 44-178-271-5444

Glan Clwyd Hospital, Rhyl, Denbighshire, Wales LL 18 5UJ, United Kingdom; Recruiting
Simon Gollins, MD, Phone: 44-1745-583-910, Email: simon.gollins@cd-tr.wales.nhs.uk

Velindre Cancer Center at Velindre Hospital, Cardiff, Wales CF14 2TL, United Kingdom; Recruiting
Laura Moss, Phone: 44-29-2031-6205

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

Starting date: November 2006
Last updated: October 6, 2009