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出境医 / 临床实验 / Cardiac Changes After Stereotactic Radiotherapy for Early Stage NSCLC Cancer (HALO)

Cardiac Changes After Stereotactic Radiotherapy for Early Stage NSCLC Cancer (HALO)

Study Description
Brief Summary:
The investigators aim to optimize the radiation treatment of early stage lung cancer patients. Therefore, detailed understanding is needed of the type of toxicity and the location of these toxicities for patients who receive high fraction doses. These have not been measured in these patients before, therefore our primary research question is: is it possible to measure changes in cardiac condition after radiotherapy, with respect to cardiac arrhythmias, fibrosis, hemodynamic function change and pericarditis?

Condition or disease Intervention/treatment Phase
Lung Cancer Stage I Lung Cancer Stage II Diagnostic Test: Cardiac condition measurements Not Applicable

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is an exploratory study to determine whether cardiac changes occur after radiation treatment. Patients are treated following standard clinical practice, with additional diagnostic investigations. The study design is therefore a cohort study.
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Cardiac Changes After Stereotactic Radiotherapy for Early Stage NSCLC Cancer
Actual Study Start Date : January 13, 2021
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023
Arms and Interventions
Arm Intervention/treatment
A
Radiotherapy; SBRT Additional cardiac diagnostics
Diagnostic Test: Cardiac condition measurements
Cardiac MRI, ECG, echocardiography, cardiac blood markers

Outcome Measures
Primary Outcome Measures :
  1. Percentage of patients with a change in cardiac condition [ Time Frame: 1 year ]
    Percentage of patients with at least 5% change in cardiac arrhythmia (outcome 2) and/or at least 5% change in fibrosis (outcome 3) and/or at least 5% change in hemodynamic function (outcome 4) and/or development of pericarditis post-treatment (outcome 5)

  2. Percentage of change in cardiac arrhythmia [ Time Frame: 1 year ]
    Percentage of change in ECG-derived QRS duration (s) between Pre- and Post-treatment values

  3. Percentage of change in fibrosis [ Time Frame: 1 year ]
    Percentage of change in MRI-derived Extra Cellular Volume (cc) between Pre- and Post-treatment values

  4. Percentage of change in hemodynamic function [ Time Frame: 1 year ]
    Percentage of change in MRI- and echocardiography-derived ejection fraction (%) between Pre- and Post-treatment values

  5. Binary change in pericarditis status [ Time Frame: 1 year ]
    Presence of pericarditis signs on MRI post-treatment while absence of pericarditis signs pre-treatment: yes/no


Secondary Outcome Measures :
  1. Local fibrosis [ Time Frame: 1 year ]
    Is there a correlation between the presence of local fibrosis and dose to this region

  2. Morphology changes [ Time Frame: 1 year ]
    Are changes in morphology visible on the MRI scans made during treatment, compared to the pre treatment MRIs


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Receive SBRT treatment for stage 1A-2B NSCLC
  • Closest distance between edge of tumor and heart < 3 cm

Exclusion Criteria:

  • Pacemaker/ICD
  • Renal function below GFR <60 ml/min/1.7m2
Contacts and Locations

Contacts
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Contact: Jose Belderbos, MD, PhD +31 20 512 9111 j.belderbos@nki.nl
Contact: Barbara Stam, PhD +31 20 512 9111 b.stam@nki.nl

Locations
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Netherlands
Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066CX
Contact: Jose Belderbos, MD, PhD    +31 20 512 9111    j.belderbos@nki.nl   
Contact: Barbara Stam, PhD    +31 20 512 9111    b.stam@nki.nl   
Principal Investigator: José Belderbos, MD, PhD         
Amsterdam UMC, location AMC Recruiting
Amsterdam, Netherlands, 1105AZ
Contact: Edith Dieleman, MD    +31205669111    e.m.dieleman@amc.uva.nl   
Leids Universitair Medisch Centrum (LUMC) Not yet recruiting
Leiden, Netherlands, 2333ZA
Contact: Krista van Doorn-Wink, MD/PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Dutch Cancer Society
Investigators
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Principal Investigator: Jose Belderbos, MD, PhD The Netherlands Cancer Institute
Tracking Information
First Submitted Date  ICMJE May 21, 2019
First Posted Date  ICMJE June 12, 2019
Last Update Posted Date February 18, 2021
Actual Study Start Date  ICMJE January 13, 2021
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
  • Percentage of patients with a change in cardiac condition [ Time Frame: 1 year ]
    Percentage of patients with at least 5% change in cardiac arrhythmia (outcome 2) and/or at least 5% change in fibrosis (outcome 3) and/or at least 5% change in hemodynamic function (outcome 4) and/or development of pericarditis post-treatment (outcome 5)
  • Percentage of change in cardiac arrhythmia [ Time Frame: 1 year ]
    Percentage of change in ECG-derived QRS duration (s) between Pre- and Post-treatment values
  • Percentage of change in fibrosis [ Time Frame: 1 year ]
    Percentage of change in MRI-derived Extra Cellular Volume (cc) between Pre- and Post-treatment values
  • Percentage of change in hemodynamic function [ Time Frame: 1 year ]
    Percentage of change in MRI- and echocardiography-derived ejection fraction (%) between Pre- and Post-treatment values
  • Binary change in pericarditis status [ Time Frame: 1 year ]
    Presence of pericarditis signs on MRI post-treatment while absence of pericarditis signs pre-treatment: yes/no
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
  • Local fibrosis [ Time Frame: 1 year ]
    Is there a correlation between the presence of local fibrosis and dose to this region
  • Morphology changes [ Time Frame: 1 year ]
    Are changes in morphology visible on the MRI scans made during treatment, compared to the pre treatment MRIs
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiac Changes After Stereotactic Radiotherapy for Early Stage NSCLC Cancer
Official Title  ICMJE Cardiac Changes After Stereotactic Radiotherapy for Early Stage NSCLC Cancer
Brief Summary The investigators aim to optimize the radiation treatment of early stage lung cancer patients. Therefore, detailed understanding is needed of the type of toxicity and the location of these toxicities for patients who receive high fraction doses. These have not been measured in these patients before, therefore our primary research question is: is it possible to measure changes in cardiac condition after radiotherapy, with respect to cardiac arrhythmias, fibrosis, hemodynamic function change and pericarditis?
Detailed Description

Rationale: For lung cancer patients that receive thoracic irradiation, cardiac toxicity was not considered to play a role, because it was expected to occur many years after treatment. However, recently several studies have shown higher death rates for lung cancer patients receiving higher cardiac doses, possibly due to cardiac toxicity. Most knowledge on cardiac toxicity that is available, is based on patients that receive conventionally fractionated radiation treatment, where the heart receives a relatively low dose of radiation. For patients that receive stereotactic body radiation therapy (SBRT), which gives high fraction doses, the heart may receive peak doses of radiation, especially for centrally located lung tumours. This type of therapy is standard of care for early stage lung cancer patients, with very high local control that is similar to surgically treated patients. In order to improve the radiation treatment for these early stage lung cancer patients, detailed knowledge on cardiac toxicity in these patients is necessary.

Objective: the investigators aim to optimize the radiation treatment of early stage lung cancer patients. To reach that goal, detailed understanding is needed of the type of toxicity and the location on the heart of these toxicities for patients who receive high fraction doses. These have not been measured in this category of patients before, therefore our primary research question is: is it possible to measure changes in cardiac condition 3 or 12 months after radiotherapy, with respect to cardiac arrhythmias, tissue fibrosis, hemodynamic function change and pericarditis? Our secondary research question is: is it possible to measure local fibrosis and correlate this to local dose? The third research question is: is it possible to measure early cardiac morphology changes during the course of the irradiation? Study design: Twenty five patients with early stage lung cancer who are treated with SBRT will be enrolled in an observational prospective cohort study and treated following standard clinical practice on a cone-beam or MR guided linear accelerator (Linac). Condition of the heart will be examined before treatment using ECG, cardiac MRI with added T1- and T2-mapping, echocardiography and blood biomarkers. These tests will be repeated 3 and 12 months after treatment.

Study population: 25 patients (stage IA-IIB) with a tumour in close proximity to the heart (edge of tumour <3cm from the heart) will be included.

Intervention (if applicable): not applicable Main study parameters/endpoints: It will be investigated 1) if changes in cardiac condition (cardiac arrhythmias, fibrosis, hemodynamic function change and pericarditis) can be visualised and quantified. A negative change of more than 5% between pre-and post-treatment measurements is considered toxicity. 2) If local fibrosis is associated to local dose, 3) if morphology changes are visible during treatment.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The patient will have 3 sessions with several diagnostic tests: ECGs, cardiac MRIs, echocardiography and blood sampling, and will fill out 3 questionnaires. Limited side effects of these tests are expected. Cardiac tests will be evaluated by a cardiologist and dedicated radiologist and reported to the radiation oncologist who will inform the patient and refer to the cardiologist if needed. The burden for these patients will be, next to the time spent for the diagnostic tests and travel time; an intravenous blood sampling and administration of MRI contrast agent. The additional time spent for diagnostic tests per session are: echo (30 min), ECG (5 min), vena puncture (5 min) and MRI (45 min) + time in the waiting room. Filling out the 3 questionnaires will take 15 min each. The possible benefit for the patient is the extensive cardiac screening. Should a problem come to light, the patient will be referred to the cardiologist.

Results from this patient cohort are directly relatable to all early stage NSCLC who are treated with SBRT, and possibly oesophageal cancer patients as well. Should this study show that cardiac dose causes cardiac toxicity in this time frame, the aim should be to improve treatment for all patients who are comparable. Ergo, patients who receive cardiac dose because of their tumour location, and who are generally unfit for surgery because of their physical condition (early stage NSCLC patients and oesophageal cancer patients).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is an exploratory study to determine whether cardiac changes occur after radiation treatment. Patients are treated following standard clinical practice, with additional diagnostic investigations. The study design is therefore a cohort study.
Masking: None (Open Label)
Primary Purpose: Screening
Condition  ICMJE
  • Lung Cancer Stage I
  • Lung Cancer Stage II
Intervention  ICMJE Diagnostic Test: Cardiac condition measurements
Cardiac MRI, ECG, echocardiography, cardiac blood markers
Study Arms  ICMJE A
Radiotherapy; SBRT Additional cardiac diagnostics
Intervention: Diagnostic Test: Cardiac condition measurements
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 11, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Receive SBRT treatment for stage 1A-2B NSCLC
  • Closest distance between edge of tumor and heart < 3 cm

Exclusion Criteria:

  • Pacemaker/ICD
  • Renal function below GFR <60 ml/min/1.7m2
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jose Belderbos, MD, PhD +31 20 512 9111 j.belderbos@nki.nl
Contact: Barbara Stam, PhD +31 20 512 9111 b.stam@nki.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03984019
Other Study ID Numbers  ICMJE M19CCR
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No data will be shared
Responsible Party The Netherlands Cancer Institute
Study Sponsor  ICMJE The Netherlands Cancer Institute
Collaborators  ICMJE Dutch Cancer Society
Investigators  ICMJE
Principal Investigator: Jose Belderbos, MD, PhD The Netherlands Cancer Institute
PRS Account The Netherlands Cancer Institute
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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