Clinical trial NCT04305613: Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated with Chemoradiation Therapy
Official title: Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated with Chemoradiation Therapy: a Prospective Longitudinal Cohort
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Cardiotoxicity
Lung Cancer Stage III
Lung Cancer Stage II
Radiation Toxicity
Keywords: Radiation Therapy Cardiotoxicity
Cardiovascular Risk Factors
Lung Cancer
Cardiovascular Phenotyping
Radiation Therapy
Cardiovascular Disease
Cardio-Oncology
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2020-03-12
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with lung cancer will be enrolled from the radiation oncology clinics at participating sites.

Brief 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: High Sensitivity C-Reactive Protein
timeFrame: up to 12 months
measure: Growth Differentiation Factor 15
timeFrame: up to 12 months
measure: Placental Growth Factor
timeFrame: up to 12 months
measure: Left Ventricular Strain
timeFrame: up to 12 months
measure: Ventricular Arterial Coupling
timeFrame: up to 12 months
measure: Coronary Flow Reserve (CFR_
timeFrame: 6 months
measure: Overall Survival (2 Year)
timeFrame: 24 months
measure: Cardiovascular Specific Mortality (2 Year)
timeFrame: 24 Months
measure: Major Cardiovascular Events (2 Year)
timeFrame: up to 24 months
Secondary outcomes:
measure: High-Sensitivity Troponin T
timeFrame: up to 12 months
measure: N-type pro Brain Natriuretic Peptide
timeFrame: up to 12 months
measure: Left Ventricular Ejection Fraction (2D)
timeFrame: up to 12 months
measure: Right Ventricular Fractional Area Change (RAC)
timeFrame: up to 12 months
measure: Right Ventricular Longitudinal Strain
timeFrame: up to 12 months
measure: Circumferential Strain
timeFrame: up to 12 months
measure: Diastolic Function
timeFrame: up to 12 months
measure: Valvular Disease
timeFrame: up to 12 months
measure: Left Ventricular Ejection Fraction (3D)
timeFrame: up to 12 months
measure: Left Ventricular systolic strain (3D)
timeFrame: up to 12 months
measure: Left Ventricular Twist and Torsion
timeFrame: up to 12 months
measure: Global and Regional Myocardial Blood Flow at Rest
timeFrame: up to 6 months
measure: Global and Regional Myocardial Blood Flow at Stress
timeFrame: up to 6 months
measure: FACIT Fatigue Score
timeFrame: up to 5 years
measure: FACIT Dyspnea Score
timeFrame: up to 5 years
measure: Godin Leisure Time Exercise Score
timeFrame: up to 5 years
Other outcomes:
measure: Overall Survival (5 Year)
timeFrame: 5-8 years
measure: Cardiovascular Specific Mortality (5 Year)
timeFrame: 5-8 Years
measure: Major Cardiovascular Events (5 Year)
timeFrame: 5 years
measure: NCI Patient Reported Outcomes Common Terms and Criteria for Adverse Events (PRO-CTCAE)
timeFrame: 5 Years
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Boston
country: United States
facility: The Brigham and Women's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: Rutger's University / Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: West Chester
country: United States
facility: Chester County Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Bonnie Ky, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References: