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
- Are there results?
- Not yet: the study is under way
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.
- More trials run by University Medical Center GroningenThe 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
- 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
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiopulmonary Toxicity of Thoracic Radiotherapy
- ClinicalTrials.gov ID
- NCT03978377
- Acronym / sponsor ID
- CLARIFY / CLARIFY
- Conditions
- Oesophageal Cancer, Non Small Cell Lung Cancer
- Keywords
- Radiotherapy, Pulmonary hypertension
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 1 Apr 2027 (estimated)
- First posted
- 7 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of patients with high risk of pulmonary hypertension
Time frame: 1 year
High-risk pulmonary hypertension according to ESC/ERS classification
6 secondary outcomes
Troponine T change
Time frame: 1 year
NTproBNP change
Time frame: 1 year
Number of patients with intermediate risk of pulmonary hypertension
Time frame: 1 year
Cumulative incidence of other late cardiopulmonary toxicity, as classified by CTCAE4.0
Time frame: 1 year
EORTC quality of life questionnaire C30
Time frame: 1 year
EORTC quality of life questionnaire LC13
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Oesophageal Cancer and Non Small Cell Lung Cancer, run by University Medical Center Groningen at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact CT Muijs, MD PhD (00315036115179, c.t.muijs@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with high risk of pulmonary hypertension (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.