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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT00415233
First received: December 20, 2006
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Biological: recombinant thyroid-stimulating hormone
Radiation: Radiodine ablation without rhTSH
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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]

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Proportion of patients with successful remnant ablation at 6-9 months [ Time Frame: 6-9 months ] [ Designated as safety issue: No ]
    The percentage of patients who have a successful remnant ablation at 6-9 months after radioiodine administration.


Secondary Outcome Measures:
  • Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months [ Time Frame: Baseline to 3 months ] [ Designated as safety issue: No ]
    Quality of life as measured by the SF-36 questionnaire at baseline, the day of ablation, and at 3 months

  • Locoregional recurrence [ Time Frame: During and post treatment ] [ Designated as safety issue: No ]
  • Distant metastases [ Time Frame: Baseline to 5 years after randomisation of final patient ] [ Designated as safety issue: No ]
    After the 5 year follow up period, patients will be follwed at hospital according to routine practice.

  • Survival [ Time Frame: Until patient death ] [ Designated as safety issue: No ]
  • Incidence of second primary malignancy [ Time Frame: Baseline to 5 years after last patient is randomised ] [ Designated as safety issue: No ]
    After the 5 year follow up period, patients will be follwed at hospital according to routine practice.


Enrollment: 438
Study Start Date: November 2006
Estimated Study Completion Date: June 2015
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1.1Gbq with rhTSH
Patients receive 1.1GBq dose of radioactive iodine and rhTSH
Biological: recombinant thyroid-stimulating hormone
Recombinant thyroid stimulating hormone (rhTSH) should be given at a dose of 0.9mg by intramuscular injection on two consecutive days before ablation.
Experimental: 3.2 GBq with rhTSH
Patients receive 3.2GBq dose of radioactive idodine and rhTSH
Biological: recombinant thyroid-stimulating hormone
Recombinant thyroid stimulating hormone (rhTSH) should be given at a dose of 0.9mg by intramuscular injection on two consecutive days before ablation.
Experimental: 1.1GBq without rhTSH
Patients only receive 1.1GBq dose of radioactive iodine and no rhTSH
Radiation: Radiodine ablation without rhTSH
Patients in this group do not receive rhTSH pre ablation.
Experimental: 3.2GBq without rhTSH
Patients only receive 3.2GBq dose of radioactive iodine and no rhTSH
Radiation: Radiodine ablation without rhTSH
Patients in this group do not receive rhTSH pre ablation.

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

Ages Eligible for Study:   16 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00415233

Locations
United Kingdom
Sussex Cancer Centre at Royal Sussex County Hospital
Brighton, England, United Kingdom, BN2 5BE
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Kent and Canterbury Hospital
Canterbury, England, United Kingdom, CT1 3NG
Castle Hill Hospital
Cottingham, England, United Kingdom, HU16 5JQ
Derbyshire Royal Infirmary
Derby, England, United Kingdom, DE1 2QY
Royal Devon and Exeter Hospital
Exeter, England, United Kingdom, EX2 5DW
Gloucestershire Royal Hospital
Gloucester, England, United Kingdom, GL1 3NN
St. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, United Kingdom, GU2 7XX
Ipswich Hospital
Ipswich, England, United Kingdom, IP4 5PD
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Guy's Hospital
London, England, United Kingdom, SE1 9RT
Royal Marsden - London
London, England, United Kingdom, SW3 6JJ
Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
James Cook University Hospital
Middlesbrough, England, United Kingdom, TS4 3BW
Newcastle Upon Tyne Hospitals NHS Trust
Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
Northampton General Hospital
Northampton, England, United Kingdom, NN1 5BD
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, United Kingdom, HA6 2RN
Norfolk and Norwich University Hospital
Norwich, England, United Kingdom, NR4 7UY
Dorset Cancer Centre
Poole Dorset, England, United Kingdom, BH15 2JB
Cancer Research Centre at Weston Park Hospital
Sheffield, England, United Kingdom, S10 2SJ
University Hospital of North Staffordshire
Stoke-On-Trent, England, United Kingdom, ST4 7LN
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
Glan Clwyd Hospital
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
Sponsors and Collaborators
University College, London
Investigators
Study Chair: Ujjal K. Mallick, MD Newcastle-upon-Tyne Hospitals NHS Trust
  More Information

No publications provided by University College, London

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT00415233     History of Changes
Other Study ID Numbers: CDR0000522490, CRUK-HILO-BRD/05/83, ISRCTN56078540, EU-20665, CTA-20363/0217/001/0001, EUDRACT-2005-003687-37
Study First Received: December 20, 2006
Last Updated: June 20, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
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

Additional relevant MeSH terms:
Thyroid Neoplasms
Head and Neck Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Endocrine System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014