Early Imaging Biomarkers in NSCLC

Early Imaging Biomarkers to Predict Radiation-Induced Cardiopulmonary Toxicity in Patients With Thoracic Malignancies

The purpose of this study is to investigate if cardiac MRI, blood biomarkers, and lung CT scans can detect early changes to the associated with radiation therapy in patients receiving radiation treatment for thoracic cancer.

Study Overview

• Status: Completed
• Conditions: Thoracic Cancer
• Intervention / Treatment: Other: Imaging Biomarkers; Other: Pulmonary; Other: Imaging; Other: Specimen Collection

Detailed Description

This study seeks to investigate the utility of novel imaging biomarkers, namely whole lung volumetric CT scans and cardiac MRI, to non-invasively identify early pathologic changes in pulmonary and cardiac function resulting from thoracic radiation. The ability to identify these changes during the course of treatment offers a powerful tool to optimize radiation dose distributions within uninvolved normal tissue by adapting treatment to the individual patient response. In addition it may lead to other therapeutic interventions designed to reduce long term cardiopulmonary toxicity.

The cardiac MRI will be performed using Aminophylline, Gadopentetate Dimeglumine and Regadenoson. These are not FDA approved for this purpose, but are being used off label and are IND exempt. Additionally, patients will be consented with an optional choice to retain research blood samples for 15 years after the completion of the study. This will allow cutting edge analysis for biomarkers that may be discovered in the future.

• Study Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing conventionally-fractionated intrathoracic radiation therapy.

Description

Inclusion Criteria:

• Patients receiving once daily fractionated intrathoracic radiation therapy for:
• Stage IIA-IIIB non-small cell lung cancer
• Limited stage small cell lung cancer
• Stage I-III esophageal cancer (neoadjuvant or definitive)
• Patients must be 18 years of age or older
• Must not be claustrophobic
• Must have adequate kidney function

Exclusion Criteria:

• Patients with small cell lung cancer receiving twice daily (b.i.d.) radiation
• Patients with esophageal cancer receiving trastuzamab
• Pregnancy or lactation
• Claustrophobia
• Inability to lie flat for 60-90 minutes
• Renal dysfunction with eGFR <60 mL/min/1.73 m2
• Allergy to gadolinium containing contrast media
• Implanted devices, metallic hazards or other conditions presenting a contraindication to 3Tesla cardiac MRI

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lung or Esophageal Patients; Patients with lung or esophageal cancer undergoing conventionally-fractionated radiation therapy. Interventions to be administered include: Imaging Biomarkers using Volumetric CT Scans, Pulmonary using Pulmonary Function Test & 6Minute Hall Walk, Imaging using Cardiac MRI, Specimen Collection using Blood Draws.	Other: Imaging Biomarkers; Whole lung volumetric CT scans; Other: Pulmonary; Pulmonary Function Tests & 6 minute hall walk; Other: Imaging; Cardiac MRI; Other: Specimen Collection; Blood draw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Lung Function	To characterize longitudinal changes in lung function using a voxel-wise image analysis technique of whole-lung CT scans in patients undergoing intrathoracic radiation therapy.	1 Year post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Myocardial Tissue	To assess longitudinal changes in myocardial tissue and coronary vasculature physiology, using cardiac MR in patients undergoing intrathoracic radiation therapy.	1 Year post treatment
Change from Baseline in Myocardial Tissue	To assess longitudinal changes in myocardial tissue and coronary vasculature physiology, including microvascular dysfunction, using cardiac MR in patients undergoing intrathoracic radiation therapy.	1 Year post treatment
Change from Baseline in Myocardial Tissue	To assess longitudinal changes in myocardial tissue and coronary vasculature physiology, including diffuse fibrosis, using cardiac MR in patients undergoing intrathoracic radiation therapy.	1 Year post treatment
Radiation Predictors from Baseline in Cardiopulmonary Changes	To explore radiation dosimetric predictors of CT- and MR-detectible cardiopulmonary changes.	1 Year post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation Induced Change from Baseline in Imaging	To determine if early imaging-based changes are associated with radiation induced pulmonary and cardiac injury at 6- and 12-months	6 month and 1 year post treatment

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: Department of Health and Human Services

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2015
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: April 14, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): August 26, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: UMCC 2015.006; HUM00097162 (Other Identifier: U-M IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No