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

• Sponsor: Abramson Cancer Center of the University of Pennsylvania (Other)
• Overall Status: Enrolling by invitation
• CT.gov ID: NCT04305613
• Collaborator: (none)
• Enrollment: 221
• Locations: 5
• Anticipated Duration (Months): 95.6
• Patients Per Site: 44.2
• Patients Per Site Per Month: 0.5

Study Details

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	Phase
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
• Anticipated 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: Sep 14, 2020
• Anticipated Primary Completion Date: Sep 1, 2025
• Anticipated Study Completion Date: Sep 1, 2028

Arms and Interventions

Arm

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 [up to 12 months]

   Change in hsCRP from baseline

2. Growth Differentiation Factor 15 [up to 12 months]

   Change in GDF-15 from baseline

3. Placental Growth Factor [up to 12 months]

   Change in PIGF from baseline

4. Left Ventricular Strain [up to 12 months]

   Change in echo-derived measures of LV peak systolic strain (longitudinal) from baseline

5. Ventricular Arterial Coupling [up to 12 months]

   Change in echo-derived measures of ventricular-arterial coupling (Ea/Ees) from baseline

6. Coronary Flow Reserve (CFR_ [6 months]

   Change in PET/CT derived CFR from baseline

7. Overall Survival (2 Year) [24 months]

   All-cause mortality assessed by electronic medical record (EMR) review

8. Cardiovascular Specific Mortality (2 Year) [24 Months]

   Cardiovascular specific mortality assessed by EMR review

9. Major Cardiovascular Events (2 Year) [up to 24 months]

   Incidence of MCE assessed by EMR review and patient interview

Secondary Outcome Measures

1. High-Sensitivity Troponin T [up to 12 months]

   Change in hsTnT from baseline

2. N-type pro Brain Natriuretic Peptide [up to 12 months]

   Change in NTproBNP from baseline

3. Left Ventricular Ejection Fraction (2D) [up to 12 months]

   Change in echo-derived LVEF from baseline

4. Right Ventricular Fractional Area Change (RAC) [up to 12 months]

   Change in echo-derived RAC from baseline

5. Right Ventricular Longitudinal Strain [up to 12 months]

   Change in echo-derived RV longitudinal strain from baseline

6. Circumferential Strain [up to 12 months]

   Change in echo-derived circumferential strain from baseline

7. Diastolic Function [up to 12 months]

   Change in echo-derived measures of diastolic function from baseline

8. Valvular Disease [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) [up to 12 months]

   Change in 3D echocardiography derived LVEF from baseline

10. Left Ventricular systolic strain (3D) [up to 12 months]

    Change in 3D echocardiography derived measures of LV systolic strain from baseline

11. Left Ventricular Twist and Torsion [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 [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 [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 [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 [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 [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) [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) [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) [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) [5 Years]

   Incidence of symptomatic adverse events as assessed by NCI's PRO-CTCAE

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 18 years of age

• Histologically confirmed, locally advanced Stage II, IIIA, or IIIB non-small cell lung cancer with inoperable disease

• Planned to receive treatment with definitive concurrent chemoradiation with curative intent

• Able to give written informed consent

Exclusion Criteria:

• Pregnant or breast-feeding

• Prior thoracic radiotherapy that would result in overlap of radiation therapy in the heart

• Prior treatment with anthracyclines

• 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 2nd or 3rd degree atrioventricular block without a pacemaker, or sick sinus syndrome; systolic blood pressure less than 90mmHg; known hypersensitivity to Regadenoson or adenosine; profound sinus bradycardia (heart rate less than 40bpm).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35233
2	The Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
5	Chester County Hospital	West Chester	Pennsylvania	United States	19380

Sponsors and Collaborators

• Abramson Cancer Center of the University of Pennsylvania

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04305613
• Other Study ID Numbers: UPCC 13519
• First Posted: Mar 12, 2020
• Last Update Posted: Feb 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Abramson Cancer Center of the University of Pennsylvania: Radiation Therapy Cardiotoxicity; Cardiovascular Risk Factors; Lung Cancer; Cardiovascular Phenotyping; Radiation Therapy; Cardiovascular Disease; Cardio-Oncology
• Additional relevant MeSH terms: Lung Neoplasms; Cardiotoxicity

Study Results

No Results Posted as of Feb 2, 2022