Hemithyroidectomy or Total-Thyroidectomy in 'Low-risk' Thyroid Cancers

Differentiated Thyroid Cancer Clinical Trial

— HoT  

Official title:

Hemithyroidectomy or Total-Thyroidectomy in 'Low-risk' Thyroid Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05604963
• Other study ID #: UCL/136591
• Status: Recruiting
• Phase: N/A
• Start date: February 14, 2022
• Est. completion date: July 31, 2031

Study information

• Verified date: November 2023
• Source: University College, London
• Contact: Aniqa Tasnim (UCL Cancer Trials Centre)
• Phone: 020 3108 4753
• Email: ctc.hot[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-centre, randomised, non-inferiority, phase III study in patients with low risk differentiated thyroid cancer.

Patients will be identified via oncology multidisciplinary team meetings. There will be two sources of patients in the trial, with the same histological diagnoses and prognosis (i.e. recurrence risk):

• Group 1: Patients who have already had a HT for thyroid problems and are then subsequently diagnosed with low risk DTC will be randomised 1:1 to undergo surveillance only OR a second operation to remove the rest of their thyroid gland (two-stage total thyroidectomy).

• Group 2: Patients diagnosed with low risk DTC using cytology (Thy5) but no surgery performed will be randomised 1:1 to have either a hemi-thyroidectomy OR a single-stage total thyroidectomy.

The overall aim of the trial is to determine whether hemithyroidectomy is an acceptable and cost-effective surgical procedure compared to total thyroidectomy in low risk thyroid cancer. Overall, 456 patients will be recruited to the trial. Patients will be initially be followed up post-surgery then 12 monthly for 6 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 456
• Est. completion date: July 31, 2031
• Est. primary completion date: July 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Group 1 (HT already performed prior to diagnosis)

Inclusion criteria

• Aged 16 or over

Papillary thyroid cancer:

• pT1b-2 (=4cm) irrespective of molecular genetic markers

• R0 resection (clinically excised but microscopic R1 resected tumours at discretion of the local MDT)

• cN0 or pN0, pNX & pN1a (=5 foci, no extranodal spread)

• Confined to thyroid or minimal extrathyroidal extension

• No higher risk histological variants on morphology (small foci allowed at the discretion of the local MDT)

• No angioinvasion NB. PTC is still eligible where microscopic invasion of endothelial lined small capillary vascular spaces and lymphatic channels are present. It becomes ineligible in the rare instances when there is definite invasion of a larger vascular structure such as a vein with smooth muscle in its wall.

• Encapsulated FVPTC with capsular invasion only

• Micro-PTC (=1cm)

• multifocal

• unifocal with pN1a (=5 foci; no extranodal spread)

Follicular thyroid cancer (FTC), including oncocytic or Hürthle cell carcinoma:

• pT1b-2 (=4cm) irrespective of molecular genetic markers

• Minimally invasive, with capsular invasion +/- minimal (=4 foci) vascular invasion (the latter is now called encapsulated angioinvasive and is at the discretion of the MDT)

• Confined to thyroid or minimal extrathyroidal extension

Exclusion criteria

• >4cm

• unifocal pT1a (=1cm) PTC or FTC (unless pN1a as above)

• NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features)

• Anaplastic, poorly differentiated or medullary thyroid carcinoma

• R2

• gross extrathyroidal extension

• pT4 or macroscopic tumour invasion of loco-regional tissues or structures

• pN1a with >5 foci or extranodal spread

• pN1b

• M1

• Aggressive PTC with any of the following features:

• Widely invasive

• Poorly differentiated

• Anaplastic

• predominance of Tall cell, Columnar cell, Hobnail, Diffuse sclerosing and other higher risk variants

• FTC, including oncocytic or Hürthle cell cancer with any of the following features:

• Minimally invasive with extensive vascular invasion (now called encapsulated angioinvasive) (>4 foci)

• Widely invasive

• Poorly differentiated

• Anaplastic

Group 2 (DTC on cytology or after core biopsy, who has not had prior thyroid surgery yet)

Inclusion criteria

• Aged 16 or over

• 'low risk' differentiated thyroid cancer confirmed by cytology or core biopsy.

• cT1b-2 irrespective of molecular genetic markers

• cN0

• Contralateral lobe without suspicious nodule(s) (U2, or U3/U4 with Thy2 on FNAC)

Exclusion criteria

• M1

Related Conditions & MeSH terms

• Differentiated Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Procedure:
• Total Thyroidectomy
Total Thyroidectomy - surgical removal of entire thyroid gland
• Hemithyroidectomy
Hemithyroidectomy - surgical removal of partial thyroid gland

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Royal United Hospital	Bath
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	NHS Lothian	Edinburgh
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Forth Valley Royal Hospital	Falkirk
United Kingdom	NHS Greater Glasgow & Clyde	Glasgow
United Kingdom	Ipswich Hospital	Ipswich
United Kingdom	Medway Maritime Hospital	Kent
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Liverpool University Hospitals	Liverpool
United Kingdom	Lister Hospital	London
United Kingdom	Northwick Park Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	The Royal Marsden Hospitals	London
United Kingdom	University College London Hospital	London
United Kingdom	Luton and Dunstable University Hospital	Luton
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	University Hospitals Dorset NHS Foundation Trust	Poole
United Kingdom	Queen Alexandra Hospital	Portsmouth
United Kingdom	Royal Berkshire Hospital	Reading
United Kingdom	Sheffield Teaching Hospitals	Sheffield
United Kingdom	Musgrove Park Hospital	Taunton

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3 Year Recurrence Rate	(defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first))	From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 3 years from surgery date
Secondary	5 Year Recurrence Rate	(defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first))	From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 5 years from surgery date
Secondary	Anatomical Site of Recurrence	Location of recurrence	From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date
Secondary	Risk of Loco-Regional Recurrence	(based on time to recurrence in the neck only)	From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date
Secondary	Number of Additional Investigations and Procedures after Surgery	Number of further investigations/procedures related to the patient's thyroid surgery or thyroid cancer e.g. imaging, blood test, biopsy etc.	2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery
Secondary	Type of Additional Investigations and Procedures after Surgery	Type of further investigations/procedures related to the patient's thyroid surgery or thyroid cancer e.g. imaging, blood test, biopsy etc.	2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery
Secondary	Voice Function	Measured using the Voice Handicap Index questionnaire (VHI-10); scores range from 0-40 with higher scores indicating greater voice-related handicap	Surgical complications and severity: From surgery date to discharge, 2-4 weeks, 6 months and 18 months from date of surgery; Voice Function: Post-randomisation/pre-surgery, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary	Surgical complications and severity	Using CTCAE v5.0 and the highest grade of each event type for each patient	Surgical complications and severity: From surgery date to discharge, 2-4 weeks, 6 months and 18 months from date of surgery; Voice Function: Post-randomisation/pre-surgery, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary	Requirement for Hormone Replacement Therapy	(percentage of patients who require this therapy compared between the trial arms)	From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary	Health Related Quality of Life	Measured using EORTC QLQ-C30; Scales range from 0-100 with higher scores for the functioning scales and global health status indicating higher QoL and higher scores on the symptom and single-item scales indicating lower QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary	Health Related Quality of Life	Measured using EORTC QLQ-THY35; Scales range from 0-100 with higher scores indicating higher QoL and lower scores indicating lower QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary	Health Related Quality of Life	Measured using EQ5D-5L; EQVAS score ranges from 0-100 with higher scores indicating higher QoL and lower scores indicating lower QoL; EQ-5D-5L index scores range from -0.224-1 with higher scores indicating higher QoL and lower scores indicating lower QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary	Health Related Quality of Life	Measured using FoP-Q-SF; scores range from 12-60 with higher scores indicating lower QoL and lower scores indicating higher QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary	Cost and Health Resource Use	Measured using EQ-5D-5L (generic QoL)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Secondary	Cost and Health Resource Use	Measured using EORTC QLQ-C30 (cancer-specific QoL)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Secondary	Cost and Health Resource Use	Measured using EORTC QLQ-THY34 (Cancer site specific QoL)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Secondary	Secondary Care Health Resource Use	Collected using eCRFs and retrospectively for the study period from data in the Hospital Episodes Statistics linked to records in the NCRAS	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Secondary	Primary Care Health Resource Use	Collected using eCRFs (Review of Primary Care Visits)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery