Clinical trial NCT00415233: High Dose vs Low Dose I 131 +/- rhTSH for Differentiated 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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2006-12-22
Enrollment: 438
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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)

Primary outcomes:
measure: Proportion of patients with successful remnant ablation at 6-9 months
timeFrame: 6-9 months
Secondary outcomes:
measure: Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months
timeFrame: Baseline to 3 months
measure: Locoregional recurrence
timeFrame: During and post treatment
measure: Distant metastases
timeFrame: Baseline to 5 years after randomisation of final patient
measure: Survival
timeFrame: Until patient death
measure: Incidence of second primary malignancy
timeFrame: Baseline to 5 years after last patient is randomised
Other outcomes:
Locations:
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Newcastle Upon Tyne Hospitals NHS Trust
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Rhyl
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
Study officials:
affiliation: Newcastle-upon-Tyne Hospitals NHS Trust
name: Ujjal K. Mallick, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.