Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy (CLARITY)

• ClinicalTrials.gov Identifier: NCT04305613
• Recruitment Status: Enrolling by invitation
• First Posted: March 12, 2020
• Last Update Posted: May 31, 2023
• Sponsor: Abramson Cancer Center at Penn Medicine
• Information provided by (Responsible Party): Abramson Cancer Center at Penn Medicine

Study Description

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.

Condition or disease	Intervention/treatment
Cardiotoxicity; Lung Cancer Stage III; Lung Cancer Stage II; Radiation Toxicity	Other: Chemoradiation

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 221 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy: A Prospective Longitudinal Cohort
• Actual Study Start Date: September 14, 2020
• Estimated Primary Completion Date: September 2025
• Estimated Study Completion Date: September 2028

Groups and Cohorts

Group/Cohort

Intervention/treatment

Cohort; Patients with locally advanced non-small cell lung cancer

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.

Outcome Measures

Primary Outcome Measures :

1. High Sensitivity C-Reactive Protein [ Time Frame: up to 12 months ]
   Change in hsCRP from baseline
2. Growth Differentiation Factor 15 [ Time Frame: up to 12 months ]
   Change in GDF-15 from baseline
3. Placental Growth Factor [ Time Frame: up to 12 months ]
   Change in PIGF from baseline
4. Left Ventricular Strain [ Time Frame: up to 12 months ]
   Change in echo-derived measures of LV peak systolic strain (longitudinal) from baseline
5. Ventricular Arterial Coupling [ Time Frame: up to 12 months ]
   Change in echo-derived measures of ventricular-arterial coupling (Ea/Ees) from baseline
6. Coronary Flow Reserve (CFR_ [ Time Frame: 6 months ]
   Change in PET/CT derived CFR from baseline
7. Overall Survival (2 Year) [ Time Frame: 24 months ]
   All-cause mortality assessed by electronic medical record (EMR) review
8. Cardiovascular Specific Mortality (2 Year) [ Time Frame: 24 Months ]
   Cardiovascular specific mortality assessed by EMR review
9. Major Cardiovascular Events (2 Year) [ Time Frame: up to 24 months ]
   Incidence of MCE assessed by EMR review and patient interview

Secondary Outcome Measures :

1. High-Sensitivity Troponin T [ Time Frame: up to 12 months ]
   Change in hsTnT from baseline
2. N-type pro Brain Natriuretic Peptide [ Time Frame: up to 12 months ]
   Change in NTproBNP from baseline
3. Left Ventricular Ejection Fraction (2D) [ Time Frame: up to 12 months ]
   Change in echo-derived LVEF from baseline
4. Right Ventricular Fractional Area Change (RAC) [ Time Frame: up to 12 months ]
   Change in echo-derived RAC from baseline
5. Right Ventricular Longitudinal Strain [ Time Frame: up to 12 months ]
   Change in echo-derived RV longitudinal strain from baseline
6. Circumferential Strain [ Time Frame: up to 12 months ]
   Change in echo-derived circumferential strain from baseline
7. Diastolic Function [ Time Frame: up to 12 months ]
   Change in echo-derived measures of diastolic function from baseline
8. Valvular Disease [ Time Frame: up to 12 months ]
   Change in echo-derived measures of valvular disease (degree of regurgitation or stenosis) from baseline
9. Left Ventricular Ejection Fraction (3D) [ Time Frame: up to 12 months ]
   Change in 3D echocardiography derived LVEF from baseline
10. Left Ventricular systolic strain (3D) [ Time Frame: up to 12 months ]
    Change in 3D echocardiography derived measures of LV systolic strain from baseline
11. Left Ventricular Twist and Torsion [ Time Frame: up to 12 months ]
    Change in 3D echocardiography derived measures of LV twist and torsion from baseline
12. Global and Regional Myocardial Blood Flow at Rest [ Time Frame: up to 6 months ]
    Change in PET/CT derived measures of global and regional myocardial blood flow at rest from baseline
13. Global and Regional Myocardial Blood Flow at Stress [ Time Frame: up to 6 months ]
    Change in PET/CT derived measures of global and regional myocardial blood flow at stress from baseline
14. FACIT Fatigue Score [ Time Frame: up to 5 years ]
    Change in FACIT Fatigue score from baseline. Score ranges from 0-52. Higher scores indicated less fatigue.
15. FACIT Dyspnea Score [ Time Frame: up to 5 years ]
    Change in FACIT Dyspnea score from baseline. Score ranges from 0-30. Higher scores indicate more dyspnea.
16. Godin Leisure Time Exercise Score [ Time Frame: up to 5 years ]
    Change in Godin Leisure Time Exercise Score from baseline. Higher scores indicate higher levels of physical activity.

Other Outcome Measures:

1. Overall Survival (5 Year) [ Time Frame: 5-8 years ]
   All Cause Mortality assessed by National Death Index Search performed 5 years after the last patient is enrolled.
2. Cardiovascular Specific Mortality (5 Year) [ Time Frame: 5-8 Years ]
   Cardiovascular Specific Mortality by National Death Index Search performed approximately 5 years after the final patient is enrolled.
3. Major Cardiovascular Events (5 Year) [ Time Frame: 5 years ]
   Incidence of 5-Year MCE by EMR review and patient interview
4. NCI Patient Reported Outcomes Common Terms and Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: 5 Years ]
   Incidence of symptomatic adverse events as assessed by NCI's PRO-CTCAE

Biospecimen Retention:   Samples With DNA

Plasma, Serum, and Buffy coat will be collected for planned biomarker analysis. Patients may optionally consent to have remaining blood banked for future analysis.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with lung cancer will be enrolled from the radiation oncology clinics at participating sites.

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).

Contacts and Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States, 35233

United States, Massachusetts

The Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Rutger's University / Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08901

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 190467

United States, Pennsylvania

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Chester County Hospital

West Chester, Pennsylvania, United States, 19380

Sponsors and Collaborators

Abramson Cancer Center at Penn Medicine

Investigators

• Principal Investigator: Bonnie Ky, MD, MSCE; University of Pennsylvania

More Information

• Responsible Party: Abramson Cancer Center at Penn Medicine
• ClinicalTrials.gov Identifier: NCT04305613
• Other Study ID Numbers: UPCC 13519
• First Posted: March 12, 2020
• Last Update Posted: May 31, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Participants may opt in to allowing data and/or banked samples to be used for future research and shared with other researchers. A detailed plan for sharing IPD will be finalized at a later date, and may depend in part on how many participants elect this option. Additional supporting information may be shared, including the study protocol and informed consent form.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Abramson Cancer Center at Penn Medicine:

Radiation Therapy Cardiotoxicity; Cardiovascular Risk Factors; Lung Cancer; Cardiovascular Phenotyping; Radiation Therapy; Cardiovascular Disease; Cardio-Oncology

Additional relevant MeSH terms:

Lung Neoplasms; Cardiotoxicity; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries