Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy

Radiation Toxicity Clinical Trial

— CLARITY  

Official title:

Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy: A Prospective Longitudinal Cohort

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04305613
• Other study ID #: UPCC 13519
• Status: Enrolling by invitation
• Start date: September 14, 2020
• Est. completion date: September 2028

Study information

• Verified date: May 2023
• Source: Abramson Cancer Center at Penn Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This observational cohort will evaluate the cardiovascular effects of chemoradiation used to treat locally advanced, non-small cell lung cancer. Patients will be enrolled prior to the start of therapy and followed during and for at least 2 years after therapy with echocardiograms, nuclear stress tests, blood sampling, and quality of life surveys.

Description:

Lung cancer is both the most common malignancy worldwide and the leading cause of cancer death in the US. While radiation therapy is highly effective for many solid tumors, thoracic radiation therapy carries a risk of cardiovascular morbidity and mortality that limits critical gains in cancer control and survival. The investigators will perform detailed cardiovascular phenotyping using biologic and imaging markers to define functional and physiologic perturbations that occur with radiation therapy. The study will provide insights into how cardiovascular risk factors and disease impact these biologic and functional changes. The investigators will also determine which radiotherapy dose-volume metrics are indicative of subclinical cardiotoxicity.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 221
• Est. completion date: September 2028
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At least 18 years of age
• Histologically confirmed or clinically diagnosed non-small cell lung cancer where the plan is for definitive treatment that includes radiation
• Able to give written informed consent

Exclusion Criteria:

• Pregnant or breast-feeding
• Prior treatment with anthracyclines
• Radiation treatment not expected to involve any heart exposure as determined by treating provider
• ECOG performance status greater than 2
• Vulnerable patients, including pregnant women and prisoners
• Contraindication to rest/vasodilator stress PET/CT, including: asthma with ongoing wheezing at time of enrollment; known Mobitz Type II AV block, 3rd degree AV block, or sick sinus syndrom, without a pacemaker; systolic blood pressure less than 90mmHg; known hypersensitivity to Regadenoson and adenosine; profound sinus bradycardia (heart rate less than 40bpm).

Related Conditions & MeSH terms

• Cardiotoxicity
• Lung Cancer Stage II
• Lung Cancer Stage III
• Lung Neoplasms
• Radiation Toxicity

Intervention

Other:
• Chemoradiation
Patients will be treated with definitive concurrent chemoradiation with curative intent as determined by their medical and radiation oncologists. We will consider timing of initiation and discontinuation, type, and cumulative dose of platinum based chemotherapy. We will also consider dose, duration, and type of immunotherapy. Radiation therapy will be delivered via proton or proton therapy. Our primary radiation therapy dose-volume exposures are whole heart volumetric dose. As secondary exposures, we will comprehensively define radiation therapy dose parameters to the right ventricle, entire left ventricle, left ventricle segments, coronary arteries, and mean heart dose.

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	The Brigham and Women's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Rutger's University / Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Chester County Hospital	West Chester	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abramson Cancer Center at Penn Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival (5 Year)	All Cause Mortality assessed by National Death Index Search performed 5 years after the last patient is enrolled.	5-8 years
Other	Cardiovascular Specific Mortality (5 Year)	Cardiovascular Specific Mortality by National Death Index Search performed approximately 5 years after the final patient is enrolled.	5-8 Years
Other	Major Cardiovascular Events (5 Year)	Incidence of 5-Year MCE by EMR review and patient interview	5 years
Other	NCI Patient Reported Outcomes Common Terms and Criteria for Adverse Events (PRO-CTCAE)	Incidence of symptomatic adverse events as assessed by NCI's PRO-CTCAE	5 Years
Primary	High Sensitivity C-Reactive Protein	Change in hsCRP from baseline	up to 12 months
Primary	Growth Differentiation Factor 15	Change in GDF-15 from baseline	up to 12 months
Primary	Placental Growth Factor	Change in PIGF from baseline	up to 12 months
Primary	Left Ventricular Strain	Change in echo-derived measures of LV peak systolic strain (longitudinal) from baseline	up to 12 months
Primary	Ventricular Arterial Coupling	Change in echo-derived measures of ventricular-arterial coupling (Ea/Ees) from baseline	up to 12 months
Primary	Coronary Flow Reserve (CFR_	Change in PET/CT derived CFR from baseline	6 months
Primary	Overall Survival (2 Year)	All-cause mortality assessed by electronic medical record (EMR) review	24 months
Primary	Cardiovascular Specific Mortality (2 Year)	Cardiovascular specific mortality assessed by EMR review	24 Months
Primary	Major Cardiovascular Events (2 Year)	Incidence of MCE assessed by EMR review and patient interview	up to 24 months
Secondary	High-Sensitivity Troponin T	Change in hsTnT from baseline	up to 12 months
Secondary	N-type pro Brain Natriuretic Peptide	Change in NTproBNP from baseline	up to 12 months
Secondary	Left Ventricular Ejection Fraction (2D)	Change in echo-derived LVEF from baseline	up to 12 months
Secondary	Right Ventricular Fractional Area Change (RAC)	Change in echo-derived RAC from baseline	up to 12 months
Secondary	Right Ventricular Longitudinal Strain	Change in echo-derived RV longitudinal strain from baseline	up to 12 months
Secondary	Circumferential Strain	Change in echo-derived circumferential strain from baseline	up to 12 months
Secondary	Diastolic Function	Change in echo-derived measures of diastolic function from baseline	up to 12 months
Secondary	Valvular Disease	Change in echo-derived measures of valvular disease (degree of regurgitation or stenosis) from baseline	up to 12 months
Secondary	Left Ventricular Ejection Fraction (3D)	Change in 3D echocardiography derived LVEF from baseline	up to 12 months
Secondary	Left Ventricular systolic strain (3D)	Change in 3D echocardiography derived measures of LV systolic strain from baseline	up to 12 months
Secondary	Left Ventricular Twist and Torsion	Change in 3D echocardiography derived measures of LV twist and torsion from baseline	up to 12 months
Secondary	Global and Regional Myocardial Blood Flow at Rest	Change in PET/CT derived measures of global and regional myocardial blood flow at rest from baseline	up to 6 months
Secondary	Global and Regional Myocardial Blood Flow at Stress	Change in PET/CT derived measures of global and regional myocardial blood flow at stress from baseline	up to 6 months
Secondary	FACIT Fatigue Score	Change in FACIT Fatigue score from baseline. Score ranges from 0-52. Higher scores indicated less fatigue.	up to 5 years
Secondary	FACIT Dyspnea Score	Change in FACIT Dyspnea score from baseline. Score ranges from 0-30. Higher scores indicate more dyspnea.	up to 5 years
Secondary	Godin Leisure Time Exercise Score	Change in Godin Leisure Time Exercise Score from baseline. Higher scores indicate higher levels of physical activity.	up to 5 years