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TSH Suppression During Radiotherapy on Thyroid Site to Prevent Iatrogenic Hypothyroidism in Pediatric Cancer Patients (WIN-HYPO2021)

Primary Purpose

Hypothyroidism; Irradiation

Status
Recruiting
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Levothyroxine
Sponsored by
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hypothyroidism; Irradiation

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

TSH suppression during irradiation

Any TSH suppression during irradiation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
September 14, 2021
Last Updated
April 6, 2022
Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
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1. Study Identification

Unique Protocol Identification Number
NCT05316922
Brief Title
TSH Suppression During Radiotherapy on Thyroid Site to Prevent Iatrogenic Hypothyroidism in Pediatric Cancer Patients
Acronym
WIN-HYPO2021
Official Title
Protection From Iatrogenic Hypothyroidism Patients With MBL and Pediatric Patients With HL and Non-HL Needing Radiotherapy on Thyroid Site
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2021 (Actual)
Primary Completion Date
September 30, 2029 (Anticipated)
Study Completion Date
September 30, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypothyroidism; Irradiation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective, non-blinded, randomised two cohorts study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TSH suppression during irradiation
Arm Type
Experimental
Arm Description
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.
Arm Title
Any TSH suppression during irradiation
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Levothyroxine
Other Intervention Name(s)
Thyroid drugs
Intervention Description
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.
Primary Outcome Measure Information:
Title
Hypothyroidism-free survival
Description
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.
Time Frame
3 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Any patient with medulloblastoma, Hodgkin/non-Hodgkin Lymphoma after radiotherapy including thyroid parenchyma; Not signed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maura Massimino, MD
Phone
+0390223902593
Email
maura.massimino@istitutotumori.mi.it
First Name & Middle Initial & Last Name or Official Title & Degree
Luna Boschetti
Phone
+0390223902590
Email
luna.boschetti@istitutotumori.mi.it
Facility Information:
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milan
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luna Boschetti
Phone
00390223902590
Email
luna.boschetti@istitutotumori.mi.it
First Name & Middle Initial & Last Name & Degree
Maura Massimino, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31747379
Citation
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.
Results Reference
background
PubMed Identifier
26975210
Citation
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.
Results Reference
background
PubMed Identifier
17601681
Citation
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.
Results Reference
background
PubMed Identifier
21557462
Citation
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.
Results Reference
background
PubMed Identifier
32794013
Citation
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.
Results Reference
background
Citation
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.
Results Reference
background
PubMed Identifier
3932271
Citation
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.
Results Reference
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TSH Suppression During Radiotherapy on Thyroid Site to Prevent Iatrogenic Hypothyroidism in Pediatric Cancer Patients

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