Study of levothyroxine sodium plus liothyronine sodium vs levothyroxine sodium to control TSH in advanced thyroid cancer patients on tyrosine kinase inhibitors

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What is this study about?

Patients with thyroid cancer that has spread and who have had their thyroid gland removed often develop hypothyroidism, a condition where the body lacks enough thyroid hormone. After surgery they normally take a daily pill called levothyroxine to replace the missing hormone. In this study a second hormone, liothyronine, is added for some participants, while others continue with levothyroxine alone. All participants are also receiving treatment with tyrosine kinase inhibitors, a type of medicine that helps control the growth of the cancer.

The purpose of the study is to find out whether the combination of the two hormones keeps the blood level of TSH (a test that shows how well the thyroid system is working) within the target range more often than levothyroxine by itself. Volunteers are randomly placed into one of the two medication groups at the same time they start the cancer drug. Over roughly six months they visit the clinic for regular blood checks, answer quality‑of‑life questionnaires, and are monitored for any side effects. The study looks at how often the hormone levels stay in the desired range and whether the treatment is safe.

1 enrollment and randomization

after signing the consent form, the patient is assigned a study number and the treatment group is determined by a computer system.

the patient is placed in one of two groups: lt4 alone or lt4 plus lt3.

2 receive medication and instructions

the patient receives the oral medication that matches the assigned group.

for the lt4 group, the product is levothyroxine sodium (either levotirsol oral solution or eutirox tablets) at a dose of 400 µg taken once each day.

for the combination group, the patient receives the same dose of lt4 plus liothyronine sodium (lt3) oral solution at a dose of 40 µg taken once each day.

the medication is taken by mouth with water, at the same time each day, and should not be skipped.

3 start daily medication

the patient begins the daily regimen of the assigned medication and continues it for the entire study period, which lasts 24 weeks.

the patient records each dose in a diary provided by the study.

4 first follow‑up visit (week 4)

at week 4 after starting the medication, the patient attends a clinic visit.

blood is drawn to measure tsh (thyroid‑stimulating hormone), ft3 and ft4 (free thyroid hormones), and ldl cholesterol.

the patient completes the eortc qlq‑c30 questionnaire, which assesses quality of life.

any side effects or dose changes are recorded.

5 second follow‑up visit (week 12)

at week 12, the patient returns for another clinic visit.

the same blood tests ( tsh, ft3, ft4, ldl cholesterol) are performed.

the eortc qlq‑c30 questionnaire is completed again.

the study staff checks that the medication dose has remained unchanged.

6 third follow‑up visit (week 24)

at week 24, the final scheduled visit occurs.

blood samples for tsh, ft3, ft4, and ldl cholesterol are collected.

the patient completes the last eortc qlq‑c30 questionnaire.

the overall results of the medication regimen are reviewed, and the patient is informed about the next steps in clinical care.

7 study completion

after the week‑24 visit, the patient’s participation in the trial ends.

the patient may continue or stop the medication according to the treating physician’s recommendation.

all data collected during the study are used for analysis of the primary and secondary objectives.

Who Can Join the Study?

Be at least 18 years old but younger than 80 years.
Have a diagnosis of thyroid cancer that has spread locally or to other parts of the body and is getting worse, and currently take the thyroid hormone medication LT4 (levothyroxine), and be able to start treatment with a drug called a TKI (tyrosine‑kinase inhibitor).
Have blood test results showing a thyroid‑stimulating hormone (TSH) level between 0.1 and 0.5 mIU/L (a low range that indicates the hormone dose is working).
Have an ECOG performance status of 2 or lower (a simple scale that measures how well you can carry out daily activities) and not have any sudden worsening of health in the two weeks before starting the study.
Be able to understand what the study involves, agree to follow the study procedures, and meet any other requirements the doctor decides are necessary.

Who Cannot Join the Study?

Being pregnant or breastfeeding.
Having an allergic reaction (hypersensitivity) to the study drug (investigational medicinal product) or any of its inactive ingredients (excipients).
Currently taking part in another clinical study.
Using medicines that change how the body processes thyroid hormone outside the thyroid (peripheral thyroid hormone metabolism) or medicines that block an enzyme called type 2 deiodinase (examples: amiodarone, propranolol, corticosteroids), as well as any mental‑health drugs (psychotropic medications).
Having a condition that prevents the gut from absorbing nutrients or medicines properly (malabsorption syndrome) or any other problem that affects drug absorption in the stomach or intestines (gastrointestinal tract).
Having a brain or spinal‑cord tumor that causes symptoms, or cancer that has spread to the brain or spinal cord (symptomatic primary central nervous system tumor or symptomatic CNS metastases).
Having a diagnosed mood disorder (such as depression or bipolar disorder) or any other known mental‑health condition.
Currently taking mental‑health medicines, including drugs that affect mood (psychotropic drugs), anti‑anxiety medicines (anxiolytics), or mood‑stabilizing drugs.
Having serious heart disease (cardiovascular disease), such as severe heart failure that limits activity (NYHA class III/IV heart failure) or a history of a heart attack (myocardial infarction).
Having an uncontrolled irregular fast heartbeat (atrial fibrillation) or other serious abnormal heart rhythms (arrhythmias) within the past six months.
Having serious liver problems (hepatic insufficiency) indicated by lab tests (total bilirubin higher than 2.0 mg/dL, albumin lower than 3.5 g/dL, INR higher than 1.7) or conditions such as fluid buildup in the abdomen (ascites) or brain changes due to liver disease (portosystemic encephalopathy), and/or having serious kidney problems (renal insufficiency) with an estimated filtration rate (eGFR) below 30 mL/min.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy

Other Sites

Site Name	City	Country
Fondazione Salvatore Maugeri Clinica Del Lavoro E Della Riabilitazione	Pavia	Italy
Axvaalj Oydvpaupbjo Uieydxiqyypde Swbhhr	Siena	Italy
Aogie Gtejsgluh Dj Cvvmbbk	Catania	Italy
Axslgeo Okqcausymwa Dc Plfdzst	Perugia	Italy
Upvetsfkkn Duaus Ssdam De Rotp Lu Sehyafpl	Rome	Italy
Aymhvhv Ooqddwwpqmr Uwkpdxeamdmsi Fadrcwnl Ia De Nukpgz	Naples	Italy
Aacjuwp Omtftmxnssu Umwnykfylgfij Scr Gqgwnrba Dv Dhq E Ryiqy dhhpmfqfeauhtko	Salerno	Italy
Aijricd Siztujvelxdbpt Thnueraklyrj Sdjss Pqkmo E Cytvn	Milan	Italy
Aslqaig Ohdktqnfiqc Uqfnbrajoztop Pgfoko	Pisa	Italy
Ivphcysg Opqpmlyqhu Vadlnc	Padua	Italy

Trial status

Country	Status	Recruitment Start
Italy	Not yet recruiting	04.01.2027

Trial locations

Investigated Drugs:

Levothyroxine Sodium

Levothyroxine is a synthetic form of the thyroid hormone thyroxine (T4). In this study it is used as the standard treatment (comparator) to replace the missing hormone in patients whose thyroid has been removed or damaged by cancer. Participants receive levothyroxine alone to see how well it can keep their thyroid‑stimulating hormone (TSH) levels in the desired range while they are also being treated with cancer drugs.

Liothyronine is a synthetic version of the thyroid hormone triiodothyronine (T3), which works faster than levothyroxine. In the trial it is given together with levothyroxine as a combined therapy. The goal is to find out whether adding liothyronine helps control TSH more effectively than levothyroxine alone for patients with advanced thyroid cancer who are receiving tyrosine kinase inhibitors. The medication is supplied as an oral solution or drops that can be taken by mouth.

Investigated Diseases:

Advanced thyroid carcinoma – This is a cancer that originates in the thyroid gland and has grown beyond its original site. It can spread to nearby tissues, lymph nodes, or more distant parts of the body. The tumor may start as a small nodule and gradually increase in size, sometimes invading surrounding structures. As it progresses, it can affect the normal function of the thyroid and cause changes in the neck area. The disease often follows a pattern of slow growth that can become more aggressive over time.
Post‑thyroidectomy hypothyroidism – After the thyroid gland is surgically removed, the body loses its main source of thyroid hormone. Hormone levels decline gradually as the body uses up remaining stores. Over weeks to months, individuals may notice reduced energy, slower metabolism, and increased sensitivity to cold. The deficiency becomes more evident as the hormone shortage deepens. This condition reflects the natural outcome of lacking a functional thyroid gland.

Trial ID:

2026-526113-28-00

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study of levothyroxine sodium plus liothyronine sodium vs levothyroxine sodium to control TSH in advanced thyroid cancer patients on tyrosine kinase inhibitors

What is this study about?

Who Can Join the Study?

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