Oesophageal CancerCLARIFYNCT03978377
Cardiopulmonary Toxicity of Thoracic Radiotherapy
An observational study of Oesophageal Cancer and Non Small Cell Lung Cancer, run by University Medical Center Groningen at 3 sites in 3 countries.
Trial summary
Radiotherapy improves locoregional control and survival of thoracic tumour patients. However, the associated exposure of normal tissues, often leads to side effects and possibly even reduces survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oesophageal Cancer, Non Small Cell Lung Cancer
- How many people
- 320 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 1 Sep 2018to 1 Apr 2027
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This study focuses on two patient populations: 1) Patients with oesophageal cancer in the mid or distal oesophagus, who will be treated with radiotherapy with curative intent, with or without chemotherapy, with or without surgery. 2) Patients with NSCLC stage IIA-III or NSCLC stage IV with limited brain metastases (treatable with surgery or stereotactic radiosurgery) or SCLC limited disease (stage I-IIIB), who will be treated with radiotherapy with curative intent, with or without chemotherapy. Patients will be included in 3 participating centers: * University Medical Center Groningen, Groningen, The Netherlands * Beatson West of Scotland Cancer Centre /NHS Greater Glasgow and Clyde, Glasgow, United Kingdom * Radboud UMC, Nijmegen, The Netherlands
Who may be able to join
- Patients with oesophageal cancer in the mid or distal oesophagus and patients with NSCLC stage IIA-III or NSCLC stage IV with limited brain metastases (treatable with surgery or stereotactic radiosurgery) or SCLC limited disease (stage I-IIIB)
- Scheduled for external-beam radiotherapy with curative intention.
- WHO 0-2.
- Age >= 18 years
- Written informed consent.
Who cannot join
- No heart failure in the last 2 months
- No pulmonary embolism in the last 2 months
- COPD gold IV
- BMI >35
- History of thoracic radiotherapy
- Noncompliance with any of the inclusion criteria - For MRI part: Contra indications for MRI
- For MRI part:
- contra-indications for MRI
Trial locations and contacts
3 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 3 countries
Netherlands1 site, 1 recruiting
- Recruiting
Radboud UMC
Nijmegen, Gelderland, 6525 GA
J Bussink, Prof, Dr, Jan.Bussink@radboudumc.nl
Gill McColl, Msc, 0031-24- 30 92982, Gill.McColl@radboudumc.nl
About this study
Radiotherapy improves locoregional control and survival of thoracic tumour patients. However, the associated exposure of normal tissues, often leads to side effects and possibly even reduces survival. Indeed, there is growing evidence that overall survival after radiotherapy for lung and oesophageal cancer is related to the radiation dose to heart and lungs. This suggests that thoracic radiotherapy causes mortality, which is currently not recognized as radiation-induced toxicity. So the question arises how to explain this treatment-related mortality.
Interestingly, Ghobadi et al demonstrated in rats that thoracic irradiation can lead to pulmonary hypertension (PH). Histopathological analysis showed that radiation-induced PH closely resembles the pulmonary arterial hypertension (PAH) subtype. Moreover, in a clinical pilot study we confirmed early signs of PH including dose-dependent reductions in blood flow towards the lungs in radiotherapy patients.
In general PH significantly affects survival. Moreover, the PAH subtype is the most-rapidly progressive and lethal subtype. However, medical treatment can significantly slow down PAH progression, providing opportunities for secondary prevention. Yet, hard evidence that radiation-induced PH is a clinically relevant phenomenon in patients treated for thoracic tumours, is lacking.
Read the detailed description
In the present study, the incidence and time course of treatment-related changes in cardio-pulmonary physiology will be assessed using standard diagnostic tools such as echocardiography, cardiac MRI (CMR) and serum biomarkers and relate them to the radiation dose distribution. Such insight in the characteristics of this possible radiation-induced PH and contributing risk factors is essential to develop primary (radiation dose optimization) prevention strategies.
The general objective of this study is to test the hypothesis that pulmonary hypertension (PH) is a clinically relevant radiation-induced side effect of thoracic irradiation. If confirmed this allows us to take appropriate measures in patient care to improve quality of life in thoracic cancer patients.
To investigate this hypothesis, the following specific aims have been defined:
- To assess the incidence and time course of PH in a prospective cohort study in patients treated with radiotherapy for lung or oesophageal cancer.
- To characterize other changes in myocardial function and pulmonary arteries, and their function using cardiac MR.
- To determine treatment-related risk factors, in particular radiation dose factors to the lungs and heart that could be used for future optimization strategies to minimize the risk of inducing PH in these patients.
- To determine the clinical impact by correlating PH to patient-rated outcome measure (PROMs) and survival. Taken together this study will determine if radiation-induced pulmonary hypertension is a clinically relevant toxicity and will provide information required for future studies on its prevention and treatment. In addition, more insight will be obtained on other forms of cardiovascular damage and complications that may occur in these patients.
- Conditions
- Oesophageal Cancer, Non Small Cell Lung Cancer
- Keywords
- Radiotherapy, Pulmonary hypertension
- Medical subject headings
- Esophageal Neoplasms, Carcinoma, Non-Small-Cell Lung, Hypertension, Pulmonary
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with high risk of pulmonary hypertension
High-risk pulmonary hypertension according to ESC/ERS classification
Measured: 1 year
Secondary outcomes (6)
Troponine T change
Change in Troponine T concentration, between baseline and at 1 year
Measured: 1 year
NTproBNP change
Change in NTproBNP concentration, between baseline and at 1 year
Measured: 1 year
Number of patients with intermediate risk of pulmonary hypertension
Intermediate risk of pulmonary hypertension according to ESC/ERS classification
Measured: 1 year
Cumulative incidence of other late cardiopulmonary toxicity, as classified by CTCAE4.0
Cumulative incidence of other late cardiopulmonary toxicity, as classified by CTCAE4.0
Measured: 1 year
EORTC quality of life questionnaire C30
PROMs (EORTC QoL C30), including five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting),
Measured: 1 year
EORTC quality of life questionnaire LC13
PROMs (EORTC QoL LC13), including lung cancer-associated symptoms (cough, haemoptysis, dyspnoea and site specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2019
- Study start1 Sep 2018
- Primary completion1 Apr 2026 (estimated)
- Study completion1 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oesophageal CancerStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03978377
- Sponsor's protocol ID
- CLARIFY
- Acronym
- CLARIFY
- Status last verified
- Mar 2025
- First submitted
- 1 Feb 2019
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No