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

NCT ID: NCT05316922

Last Updated: 2023-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-13

Study Completion Date

2029-09-30

Brief Summary

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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.

Detailed Description

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Patients will undergo basal thyroid ultrasound and FT3, FT4, TSH assay. Simulations with computed tomography, and computer assisted three-dimensional treatment planning with a dose volume histogram will be used to identify thyroid volumes and corresponding RT isodose distributions.

The enrolled patients will be randomly assigned (1:1) to TSH suppression group (experimental group) or non-TSH suppression group (control group). Random allocation will be managed centrally by Clinical epidemiology and Trial organization of the Fondazione IRCCS Istituto Nazionale dei Tumori. The randomization list will be generated by SAS software. Investigators and patients will not be masked to treatment allocation.

From 14 days beforehand and throughout their RT, patients in the experimental arm will receive L-thyroxine in the morning on an empty stomach (half an hour before breakfast), 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 (half dose the next day after RT, 25% the following day and stop).

Conditions

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Hypothyroidism; Irradiation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, non-blinded, randomised two cohorts study
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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TSH suppression during irradiation

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.

Group Type EXPERIMENTAL

Levothyroxine

Intervention Type 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.

Any TSH suppression during irradiation

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Levothyroxine

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.

Intervention Type DRUG

Other Intervention Names

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Thyroid drugs

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Maura Massimino, MD

Role: CONTACT

Phone: +0390223902593

Email: [email protected]

Luna Boschetti

Role: CONTACT

Phone: +0390223902590

Email: [email protected]

Facility Contacts

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Luna Boschetti

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 31747379 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26975210 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17601681 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21557462 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32794013 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 3932271 (View on PubMed)

Other Identifiers

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INT122/21

Identifier Type: -

Identifier Source: org_study_id