Health Effects of CArdiac FluoRoscopy and MOderN RadIotherapy in PediatriCs - Radiotherapy

Neoplasms Clinical Trial

— HARMONIC-RT  

Official title:

Health Effects of CArdiac FluoRoscopy and MOderN RadIotherapy in PediatriCs - Radiotherapy (HARMONIC-RT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04746729
• Other study ID #: C20-01
• Secondary ID: 2020-A01037-32/1
• Status: Recruiting
• Start date: January 11, 2021
• Est. completion date: September 30, 2040

Study information

• Verified date: January 2024
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Neige Journy, PhD
• Phone: +33 142 11 54 27
• Email: neige.journy[@]gustaveroussy.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The goal of the HARMONIC-RT study is to evaluate late health and social outcomes of contemporary techniques of external beam radiotherapy in paediatric patients, based on the setting-up of a European, long-term registry complemented by a biobank.

Description:

Specific objectives:

• To develop the infrastructure and instruments for setting-up a European, long-term registry of paediatric patients treated with contemporary techniques of modern external radiotherapy;

• To assess the incidence and severity of late health outcomes, primarily endocrine dysfunctions, cardiovascular toxicities, neurovascular damages, and subsequent primary neoplasms, in relation to the dose-volume distribution to non-targeted organs and tissues, radiation delivery technique and beam quality factors, and potential modifying factors (i.e. age at exposure, genetic predispositions, comorbidities, and systemic treatments including chemotherapy, targeted therapy, immunotherapy and hormonal drugs) that may underlie differences in individual susceptibility for these outcomes ;

• To assess societal aspects of advances in radiotherapy, primarily health-related quality of life and academic achievement, in paediatric patients treated with modern external radiotherapy techniques.

Secondary scientific objectives:

• To assess multidimensional fatigue in paediatric patients treated with modern external radiotherapy techniques, and identify clinical and therapeutic determinants of fatigue;

• To improve estimation of patient-specific doses to the whole body and non-targeted organs and substructures from different radiotherapy delivery techniques;

• To investigate radiation-induced cellular responses and biological mechanisms related to the occurrence of vascular diseases and subsequent primary neoplasms in samples of blood and saliva ; to identify biomarkers of susceptibility and health effects ; to evaluate differences in disease biomarkers in relation to the radiation delivery technique and beam quality factors ; to explore the relevance of the use of saliva as a biosampling method for paediatric cohorts regarding feasibility and the quality and reproducibility for different measured biomarkers.

Secondary strategic objectives:

• To promote sustained collaborative research activities for improvement of patient care, and inform health care providers and policy makers on the clinical and social impact of advances in radiotherapy in paediatric settings;

• To serve as a pilot for a future long-term pan-European registry of children and adolescents treated with particle and photon beam therapy, including a biobank of saliva and blood samples collected before and after treatment;

• To contribute in future collaborative projects with existing cohorts or registries in Europe

• To contribute in future international research studies on late outcomes of modern radiotherapy techniques for management of paediatric cancers

Funding: The HARMONIC project has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 847707.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2670
• Est. completion date: September 30, 2040
• Est. primary completion date: September 30, 2040
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 22 Years

Eligibility

Retrospective inclusion of study participants

Inclusion Criteria:

• First external beam radiation therapy (EBRT) started in 2000 or after for management of a first primary neoplasm

• Age under 22 years at the time of first EBRT initiation

• Radiation treatment plan (first EBRT) stored in DICOM format

• Usual residency in the country of EBRT to enable a long-term follow-up

Exclusion Criteria:

• Patients with poor prognosis (e.g. diffuse pontine glioma or high grade glioma) at first EBRT initiation

• Prior external or internal radiation therapy

• Patients who refused to participate in the study

Prospective inclusion of study participants

Inclusion Criteria:

• Scheduled first EBRT for management of a first primary neoplasm

• Age under 22 years at the time of scheduled first EBRT

• Radiation treatment plan stored in DICOM format

• Affiliate or beneficiary of health insurance (or any required equivalent as defined in applicable national law)

• Usual residency in the country of EBRT to enable a long-term follow-up

• Signed informed consent/assent

Exclusion Criteria:

• Patients with poor prognosis (e.g. diffuse pontine glioma or high grade glioma)

• Prior external or internal radiation therapy;

• Protected adults (persons under curatorship, tutorship / individuals under guardianship by court order, persons deprived of their liberty)

• Adult/parent(s)/legal representative(s) who cannot read or understand the informed consent in the applicable language(s) in the country of EBRT

Related Conditions & MeSH terms

• Neoplasms

Intervention

Other:
• No intervention
No intervention

Locations

Country	Name	City	State
Belgium	KU Leuven	Leuven
Denmark	Aarhus University hospital	Aarhus
France	Centre Régional François Baclesse	Caen
France	Gustave Roussy	Villejuif
Germany	University Hospital Essen, The West German Proton Therapy Centre Essen	Essen

Sponsors (16)

Lead Sponsor

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France

Aarhus University Hospital, Barcelona Institute for Global Health, Centre Francois Baclesse, Commissariat A L'energie Atomique, Gustave Roussy, Cancer Campus, Grand Paris, KU Leuven, Luxembourg Institute of Science and Technology, National Research Council, Institute of Clinical Physiology, Italy, Princess Maxima Center for Pediatric Oncology, Stockholm University, The West German Proton Therapy Centre, Essen, University Hospital, Essen, University Medical Center Groningen, University of Aarhus, University of Zurich

Countries where clinical trial is conducted

Belgium,  Denmark,  France,  Germany, 

References & Publications (1)

Journy N, Bolle S, Brualla L, Dumas A, Fresneau B, Haddy N, Haghdoost S, Haustermans K, Jackson A, Karabegovic S, Lassen-Ramshad Y, Thariat J, Wette MR, Botzenhardt S, De Wit I, Demoor-Goldschmidt C, Christiaens M, Hoyer M, Isebaert S, Jacobs S, Henriksen LT, Maduro JH, Ronckers C, Steinmeier T, Uyttebroeck A, Van Beek K, Walsh L, Thierry-Chef I, Timmermann B. Assessing late outcomes of advances in radiotherapy for paediatric cancers: Study protocol of the "HARMONIC-RT" European registry (NCT 04746729). Radiother Oncol. 2023 Nov 2;190:109972. doi: 10.1016/j.radonc.2023.109972. Online ahead of print. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endocrinopathies	Late health outcomes	up to 20 years after RT
Primary	Cardiovascular diseases	Late health outcomes; Neurovascular diseases; Second and subsequent primary neaoplasms	up to 20 years after RT
Primary	Neurovascular diseases	Late health outcomes	up to 20 years after RT
Primary	Second and subsequent primary neaoplasms	Late health outcomes	up to 20 years after RT
Primary	Health-related quality of life (physical, emotional, social, and school functioning) assessed by the PedsQL™ core scale (validated questionnaire)	Late social outcomes	up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
Primary	Academic achievement	Late social outcomes	up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
Secondary	Dysfunctions in endocrine hormone levels	measured as: insulin-like growth factor-1,; anterior pituitary hormones (GH, ACTH, TSH, LH, FSH),; thyroid hormones (fT3, fT4),; sexual hormones	up to 10 years after radiation therapy
Secondary	Changes in blood markers of cardiovascular diseases	measured as blood markers (incl. troponin, BNP, CPK)	up to 10 years after radiation therapy
Secondary	Changes in imaging markers of cardiovascular diseases	measured as cardiac echography parameters (incl. ejection fraction, diastolic function)	up to 10 years after radiation therapy
Secondary	Changes in imaging markers of neurovascular damages	measured as scoring of large and small vessel damages	up to 5 years after radiation therapy
Secondary	Changes in blood/saliva markers of protein activation relating to vascular damages	measured as signal quality of protein activity	up to 1 year after radiation therapy
Secondary	Changes in blood/saliva markers of oxidative stress response	measured as markers of oxidative stress (incl. 8-oxo-dG, SOD2, DNA repair enzymes)	up to 1 year after radiation therapy
Secondary	Changes in blood/saliva markers of inflammatory response	Inflammatory markers (incl. PTX3, CRP, NF-kB, IL-1 and IL10)	up to 1 year after radiation therapy
Secondary	Changes in blood/saliva markers of carcinogenesis	Markers of carcinogenesis (incl. leukocyte telomere length, mitochondrial DNA copy number, circulating microRNA)	up to 1 year after radiation therapy
Secondary	Multidimensional fatigue (general, sleep/rest, and cognitive fatigue)	PedsQL™ multidimensional fatigue scale (validated questionnaire)	up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
Secondary	Clinical events other than those mentioned as primary outcomes	Late morbidity	up to 20 years after radiation therapy
Secondary	All-cause and cause-specific mortality	Late mortality	up to 20 years after radiation therapy

External Links

•   Project's website