TSH Suppression During Radiotherapy on Thyroid Site to Prevent Iatrogenic Hypothyroidism in Pediatric Cancer Patients

NCT05316922 | Recruiting Phase 3

• 1 other identifier: INT122/21
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

To offer the possibility of a treatment that could achieve a meaningful reduction in the incidence of post-radiation therapy hypothyroidism. Thyroid dysfunction may develop from a few months to several years after patients have completed their radiation treatment. In children with chronic diseases, or given lengthy anti-neoplastic treatments, recurrent or persistent endocrine disorders may have a negative effect on growth and development into adulthood.

Conditions

Hypothyroidism; Irradiation

Outcome Measures

Primary Outcomes (1)

• Hypothyroidism-free survival

  Hypothyroidism-free survival at 3 years after radiotherapy including part or the whole thyroid parenchyma on the intention-to-treat population will be the main end-point.

  3 years

Study Arms (2)

TSH suppression during irradiation

EXPERIMENTAL

From 14 days beforehand and throughout their RT, patients in the experimental arm will receive L-thyroxine in the morning, starting with 1-2 μg/kg, and adjusting the dose every 3 days to ensure TSH \< 0.3 μIU/mL before RT beginning. The 0.3 μIU/mL threshold is just below normal range not causing hyperthyroidism, and is defined as "mild" TSH suppression. Based on hormone status, L-thyroxine doses will be gradually increased to patients' individual minimum TSH-suppressive dose before starting RT, maintained throughout the treatment, then rapidly tapered off and stopped. During radiation treatment course will be checked twice a week for serum FT3, FT4, TSH assays in order to maintain TSH \< 0.3 μIU/mL, possibly without exceeding normal levels of FT3 and FT4. Once a week patients will also have a full visit and any other blood examination according to protocol in use and Institutional practice.

Drug: Levothyroxine

Any TSH suppression during irradiation

NO INTERVENTION

Patient in the standard arm will perform radiotherapy treatment without any TSH suppression. At the end of radiation they will do serum FT3, FT4, TSH assay and then, after one year from RT, thyroid ultrasound + serum FT3, FT4, TSH assay.

Interventions

Levothyroxine DRUG

Levothyroxine is used to treat hypothyroidism (low thyroid function). This medicine is given when your thyroid does not produce enough of this hormone on its own.

Also known as: Thyroid drugs

TSH suppression during irradiation

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient with medulloblastoma, Hodgkin/non-Hodgkin Lymphoma before radiotherapy (RT) planning including thyroid parenchyma without previous primary or secondary hypothyroidism;
• Written informed consent prior to any study-specific analysis and/or data collection.

You may not qualify if:

• Any patient with medulloblastoma, Hodgkin/non-Hodgkin Lymphoma after radiotherapy including thyroid parenchyma;
• Not signed consent.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Related Publications (7)

• Prpic M, Kruljac I, Kust D, Suton P, Purgar N, Bilos LK, Gregov M, Mrcela I, Franceschi M, Djakovic N, Frobe A. Dose-volume derived nomogram as a reliable predictor of radiotherapy-induced hypothyroidism in head and neck cancer patients. Radiol Oncol. 2019 Nov 20;53(4):488-496. doi: 10.2478/raon-2019-0055.

  PMID: 31747379 BACKGROUND

• Alba JR, Basterra J, Ferrer JC, Santonja F, Zapater E. Hypothyroidism in patients treated with radiotherapy for head and neck carcinoma: standardised long-term follow-up study. J Laryngol Otol. 2016 May;130(5):478-81. doi: 10.1017/S0022215116000967. Epub 2016 Mar 15.

  PMID: 26975210 BACKGROUND

• Massimino M, Gandola L, Collini P, Seregni E, Marchiano A, Serra A, Pignoli E, Spreafico F, Pallotti F, Terenziani M, Biassoni V, Bombardieri E, Fossati-Bellani F. Thyroid-stimulating hormone suppression for protection against hypothyroidism due to craniospinal irradiation for childhood medulloblastoma/primitive neuroectodermal tumor. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):404-10. doi: 10.1016/j.ijrobp.2007.03.028. Epub 2007 Jul 2.

  PMID: 17601681 BACKGROUND

• Massimino M, Gandola L, Pignoli E, Seregni E, Marchiano A, Pecori E, Catania S, Cefalo G. TSH suppression as a possible means of protection against hypothyroidism after irradiation for childhood Hodgkins lymphoma. Pediatr Blood Cancer. 2011 Jul 15;57(1):166-8. doi: 10.1002/pbc.22915. Epub 2011 Feb 9.

  PMID: 21557462 BACKGROUND

• Massimino M, Podda M, Gandola L, Pignoli E, Seregni E, Morosi C, Spreafico F, Ferrari A, Pecori E, Terenziani M. Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study. Front Med. 2021 Feb;15(1):101-107. doi: 10.1007/s11684-020-0752-2. Epub 2020 Aug 13.

  PMID: 32794013 BACKGROUND

• Groover TA, Christie AC, Merritt EA, Coe FO, McPeak EM. Roentgen irradiation in the treatment of hyperthyroidism: a statistical evaluation based on three hundred and five cases. JAMA 1929; 92:1730-1734.

  BACKGROUND

• Bantle JP, Lee CK, Levitt SH. Thyroxine administration during radiation therapy to the neck does not prevent subsequent thyroid dysfunction. Int J Radiat Oncol Biol Phys. 1985 Nov;11(11):1999-2002. doi: 10.1016/0360-3016(85)90283-4.

  PMID: 3932271 BACKGROUND

MeSH Terms

Conditions

Hypothyroidism

Interventions

Thyroxine; Antithyroid Agents

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Maura Massimino, MD

CONTACT

+0390223902593; maura.massimino@istitutotumori.mi.it

Luna Boschetti

CONTACT

+0390223902590; luna.boschetti@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, non-blinded, randomised two cohorts study

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: April 7, 2022
• Study Start: December 13, 2021
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)