NeoplasmsHARMONIC-RTNCT04746729
Health Effects of CArdiac FluoRoscopy and MOderN RadIotherapy in PediatriCs - Radiotherapy
An observational study of Neoplasms, run by Institut National de la Santé Et de la Recherche Médicale, France at 5 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages Up to 22 years
- Conditions the study is for
- Neoplasms
- How many people
- 2,670 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 11 Jan 2021to 2 Jan 2042
- How long will I take part?
- 20 Years
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children, adolescents and young adults treated with external beam radiation therapy for a first primary neoplasm
Who may be able to join
- 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
- Scheduled first EBRT for management of a first primary neoplasm
- Age under 22 years at the time of scheduled first EBRT
Show all 10Show fewer
- 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
Who cannot join
- 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
- 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
Trial locations and contacts
5 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 4 countries
France2 sites, 2 recruiting
- Recruiting
Centre Régional François Baclesse
Caen
Juliette Thariat, MD, j.thariat@baclesse.unicancer.fr
Juliette Thariat, MD
- Recruiting
Gustave Roussy
Villejuif
Stéphanie Bolle, Stephanie.Bolle@gustaveroussy.fr
Stéphanie Bolle
Belgium1 site, 1 recruiting
- Recruiting
KU Leuven
Leuven
Sofie Isebaert, sofie.isebaert@uzleuven.be
Karin Haustermans
Denmark1 site, 1 recruiting
- Recruiting
Aarhus University hospital
Aarhus
Yasmin Lassen, yasmin.lassen@auh.rm.dk
Yasmin Lassen
Germany1 site, 1 recruiting
- Recruiting
University Hospital Essen, The West German Proton Therapy Centre Essen
Essen
Martina Wette, martina.wette@uk-essen.de
Beate Timmermann
About this study
Official title: Health Effects of CArdiac FluoRoscopy and MOderN RadIotherapy in PediatriCs - Radiotherapy (HARMONIC-RT)
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.
Read the detailed 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.
- Conditions
- Neoplasms
- Being tested
- No intervention
- Keywords
- Radiotherapy, Oncology, Paediatrics, Late toxicities, Radiation-induced neoplasms, Radiation-induced vascular damages, Radiation-induced cardiac damages, Radiation-induced endocrine damages, Quality of life, Social outcomes, External beam radiotherapy, Photon therapy, Proton therapy, Cohort, Registry
- Medical subject headings
- Neoplasms, Neoplasms, Radiation-Induced
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
What is being measured
The primary outcome is the main question the study is designed to answer.
Endocrinopathies
Late health outcomes
Measured: up to 20 years after RT
Cardiovascular diseases
Late health outcomes
- Neurovascular diseases
- Second and subsequent primary neaoplasms
Measured: up to 20 years after RT
Neurovascular diseases
Late health outcomes
Measured: up to 20 years after RT
Second and subsequent primary neaoplasms
Late health outcomes
Measured: up to 20 years after RT
Health-related quality of life (physical, emotional, social, and school functioning) assessed by the PedsQL™ core scale (validated questionnaire)
Late social outcomes
Measured: up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
Academic achievement
Late social outcomes
Measured: up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
Secondary outcomes (11)
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
Measured: up to 10 years after radiation therapy
Changes in blood markers of cardiovascular diseases
measured as blood markers (incl. troponin, BNP, CPK)
Measured: up to 10 years after radiation therapy
Changes in imaging markers of cardiovascular diseases
measured as cardiac echography parameters (incl. ejection fraction, diastolic function)
Measured: up to 10 years after radiation therapy
Changes in imaging markers of neurovascular damages
measured as scoring of large and small vessel damages
Measured: up to 5 years after radiation therapy
Changes in blood/saliva markers of protein activation relating to vascular damages
measured as signal quality of protein activity
Measured: up to 1 year after radiation therapy
Changes in blood/saliva markers of oxidative stress response
measured as markers of oxidative stress (incl. 8-oxo-dG, SOD2, DNA repair enzymes)
Measured: up to 1 year after radiation therapy
Changes in blood/saliva markers of inflammatory response
Inflammatory markers (incl. PTX3, CRP, NF-kB, IL-1 and IL10)
Measured: up to 1 year after radiation therapy
Changes in blood/saliva markers of carcinogenesis
Markers of carcinogenesis (incl. leukocyte telomere length, mitochondrial DNA copy number, circulating microRNA)
Measured: up to 1 year after radiation therapy
Multidimensional fatigue (general, sleep/rest, and cognitive fatigue)
PedsQL™ multidimensional fatigue scale (validated questionnaire)
Measured: up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
Clinical events other than those mentioned as primary outcomes
Late morbidity
Measured: up to 20 years after radiation therapy
All-cause and cause-specific mortality
Late mortality
Measured: up to 20 years after radiation therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2021
- Study start11 Jan 2021
- Primary completion30 Jan 2032 (estimated)
- Study completion2 Jan 2042 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 2,670 participants (estimated)
- Target duration
- 20 Years
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- Barcelona Institute for Global Health, The West German Proton Therapy Centre, Essen, Gustave Roussy, Cancer Campus, Grand Paris, Centre Francois Baclesse, KU Leuven, University of Aarhus, Princess Maxima Center for Pediatric Oncology, University Medical Center Groningen, Stockholm University, National Research Council, Institute of Clinical Physiology, Italy, University of Zurich, Commissariat A L'energie Atomique, Luxembourg Institute of Science and Technology, University Hospital, Essen, Aarhus University Hospital
- Responsible party
- Sponsor
- Investigators
- Beate Timmermann, MD, Principal investigator, UK EssenNeige Journy, PhD, Principal investigator, Institut National de la Santé Et de la Recherche Médicale, FranceStéphanie Bolle, MD, Principal investigator, Gustave Roussy, Cancer Campus, Grand ParisIsabelle Thierry-chef, PhD, Study chair, Barcelona Institute for Global Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04746729
- Sponsor's protocol ID
- C20-01
- Other IDs
- 2020-A01037-32/1
- Acronym
- HARMONIC-RT
- Status last verified
- Jul 2026
- First submitted
- 14 Sep 2020
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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. 2024 Jan;190:109972. doi: 10.1016/j.radonc.2023.109972. Epub 2023 Nov 2. No abstract available.
PubMed 37922994