Prospective, multicenter, randomized study on combined LT4 + LT3 therapy versus LT4 in the control of TSH in patients with advanced thyroid cancer treated with tyrosine kinase inhibitors.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ceinge Biotecnologie Avanzate Franco Salvatore S.c.a.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-26

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Evaluate the efficacy of LT4 + LT3 combination therapy compared with LT4 monotherapy in controlling TSH in patients with advanced thyroid cancer after the initiation of systemic therapy with TKIs.

Secondary objectives 6

1. Evaluate whether combined LT4 + LT3 therapy, compared with LT4 monotherapy, leads to a different longitudinal trend in FT3 and FT4 over the 24 weeks following the initiation of TKI therapy.
2. Evaluate differences in quality of life between patients treated with combined LT4 + LT3 therapy and those receiving LT4 monotherapy during TKI therapy.
3. Evaluate the potential association between changes in serum thyroid hormone levels and a peripheral thyroid hormone metabolism parameter (i.e. LDL cholesterol).
4. Evaluate the potential association between changes in serum thyroid hormone levels and the Thr92Ala polymorphism of the DIO2 gene.
5. Assess the safety of the treatments, with particular focus on cardiovascular and neuropsychiatric events related to thyroid hormone excess.
6. Assess the stability of TSH control in the two treatment arms.

Conditions and MedDRA coding

Advanced thyroid carcinoma. Post-thyroidectomy hypothyroidism.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥18 and <80 years.
2. Patients with a diagnosis of locally advanced/metastatic progressive thyroid cancer, on LT4 therapy, eligible for TKI treatment.
3. Circulating TSH levels between 0.1 and 0.5 mIU/L.
4. ECOG performance status ≤2, with no sudden deterioration in the two weeks prior to the start of the study.
5. Patients able to understand the full nature and purpose of the study, including potential risks and side effects, able to comply with study procedures, and meet all study requirements according to the investigator’s judgment.

Exclusion criteria 11

1. Pregnancy or breastfeeding.
2. Use of drugs interfering with peripheral thyroid hormone metabolism or known type 2 deiodinase inhibitors (e.g., amiodarone, propranolol, corticosteroids) and psychotropic medications.
3. Clinically significant active malabsorption syndrome or other conditions affecting gastrointestinal drug absorption.
4. Symptomatic primary central nervous system tumor or symptomatic CNS metastases.
5. Psychiatric diagnosis of mood disorder or other known psychiatric conditions.
6. Treatment with psychotropic drugs, anxiolytics, or mood stabilizers.
7. Clinically significant active cardiovascular disease (e.g., NYHA class III/IV heart failure) or history of myocardial infarction.
8. Uncontrolled atrial fibrillation or clinically significant arrhythmias in the past 6 months.
9. Epatic insufficiency (total bilirubin >2.0 mg/dL, albumin <3.5 g/dL, INR >1.7, ascites, portosystemic encephalopathy) and/or renal insufficiency (eGFR <30 mL/min).
10. Hypersensitivity to the investigational medicinal product or its excipients.
11. Participation in other clinical studies.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number and proportion of patients in each group who maintain TSH within the target range (0.1–0.5 mIU/L) throughout the study without any dose adjustments of LT4 and/or LT3.

Secondary endpoints 7

1. Absolute change from baseline in serum FT3 and FT4 concentrations (ΔFT3, ΔFT4) at weeks 4, 12, and 24 after TKI initiation.
2. Absolute change from baseline in EORTC QLQ–C30 v3.0 questionnaire scores at weeks 4, 12, and 24 after TKI initiation.
3. Change from baseline in LDL cholesterol at weeks 4, 12, and 24 after TKI initiation.
4. Association between changes in serum thyroid hormone levels and the Thr92Ala polymorphism of the DIO2 gene.
5. Treatment safety, with reference to the duration of excessive TSH suppression (TSH <0.1 mIU/L) and time spent outside the target range (TSH >0.5 mIU/L).
6. Time to first TSH deviation above the target range (TSH >0.5 mIU/L) after the initiation of TKI.
7. Percentage of time serum TSH values remain within the target range (0.1–0.5 mIU/L) after the initiation of TKI.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ceinge Biotecnologie Avanzate Franco Salvatore S.c.a.r.l.

Sponsor organisation

Ceinge Biotecnologie Avanzate Franco Salvatore S.c.a.r.l.

Address

Via Gaetano Salvatore 486

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Ceinge Biotecnologie Avanzate Franco Salvatore S.c.a.r.l.

Contact name

Domenico Salvatore

Public contact point

Organisation

Ceinge Biotecnologie Avanzate Franco Salvatore S.c.a.r.l.

Contact name

Domenico Salvatore

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications