Mitigation of Radiation Pneumonitis and Fibrosis

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

This project will test the effect of enalapril to mitigate the lung damage that can occur as a side effect of radiation therapy for lung cancer or other intrathoracic cancers. Thousands of Veterans develop lung cancer every year, and are treated by radiation therapy. Studies of lung radiation injury in laboratory animals show that with enalapril, investigators can significantly reduce the severity of radiation injury to the lung. Enalapril is FDA approved and in common use for treatment of hypertension, kidney disease, and heart failure. These studies will advance that work to human use. Successful mitigation of lung radiation damage will improve the quality of life in Veterans and non-Veterans who are treated for lung cancer by radiation, and may also improve cure rates of radiation therapy for lung cancer.

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Radiation Pneumonitis	Drug: Enalapril; Drug: placebo	Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	200 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Care Provider)
Primary Purpose:	Prevention
Official Title:	Mitigation of Radiation Pneumonitis and Fibrosis
Actual Study Start Date :	November 1, 2013
Estimated Primary Completion Date :	January 31, 2020
Estimated Study Completion Date :	January 31, 2020

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: enalapril; Use of enalapril in subjects undergoing radiotherapy for lung cancer.	Drug: Enalapril; Enalapril once a day, orally, as 2.5 , 5, or 10 mg tablets to be given in escalating doses, to subjects undergoing radiotherapy for lung cancer
Placebo Comparator: placebo; Use of placebo in subjects undergoing radiotherapy for lung cancer	Drug: placebo; Placebo, once a day, orally, as 2.5 , 5, or 10 mg tablets to be given in escalating doses, to subjects undergoing radiotherapy for lung cancer

Outcome Measures

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Primary Outcome Measures :

1. Radiation pneumonitis [ Time Frame: one year ]
   The clinical occurrence and grade of radiation pneumonitis, by National Cancer Institute Common Terminology Criteria Adverse Event grading ( NCI CTCAE)

Secondary Outcome Measures :

1. Radiation pneumonitis [ Time Frame: one year ]
   The occurrence and grade of radiation pneumonitis by radiographic criteria, using CT scanning
2. Radiation fibrosis [ Time Frame: one year ]
   The occurrence and grade of radiation fibrosis by radiographic criteria, using CT scanning
3. Cancer recurrence and cancer-related survival [ Time Frame: two years ]
   The recurrence of lung cancer after radiation therapy and the cancer-related survival after radiation therapy, in subjects taking enalapril compared to those on placebo drug.

Eligibility Criteria

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Ages Eligible for Study:	35 Years to 85 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Men and women undergoing radiation therapy to the chest for cancer at the Baltimore, the Milwaukee, and Ann Arbor Veterans Affairs Hospital are eligible.
• Subjects who require radiation therapy to attempt to cure or to palliate their disease will be eligible for this study.

Exclusion Criteria:

• Subjects eligible for surgical resection and who do not need radiation therapy will not be eligible for this study.
• Subjects who must remain on ACE inhibitors, angiotensin blockers, or renin antagonists will be excluded.

Contacts and Locations

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Locations

United States, Maryland
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
Baltimore, Maryland, United States, 21201
United States, Michigan
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, United States, 48105
United States, Wisconsin
Clement J. Zablocki VA Medical Center, Milwaukee, WI
Milwaukee, Wisconsin, United States, 53295-1000

Sponsors and Collaborators

VA Office of Research and Development

Investigators

Principal Investigator:	Eric Phin Cohen, MD	Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

More Information

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Publications of Results:

Kharofa J, Cohen EP, Tomic R, Xiang Q, Gore E. Decreased risk of radiation pneumonitis with incidental concurrent use of angiotensin-converting enzyme inhibitors and thoracic radiation therapy. Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):238-43. doi: 10.1016/j.ijrobp.2011.11.013. Epub 2012 Jan 31.

Citrin DE, Prasanna PGS, Walker AJ, Freeman ML, Eke I, Barcellos-Hoff MH, Arankalayil MJ, Cohen EP, Wilkins RC, Ahmed MM, Anscher MS, Movsas B, Buchsbaum JC, Mendonca MS, Wynn TA, Coleman CN. Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016. Radiat Res. 2017 Jul;188(1):1-20. doi: 10.1667/RR14784.1. Epub 2017 May 10.

Responsible Party:	VA Office of Research and Development
ClinicalTrials.gov Identifier:	NCT01754909 History of Changes
Other Study ID Numbers:	CLIN-004-12S; 1I01CX000569-01A2 ( U.S. NIH Grant/Contract )
First Posted:	December 21, 2012
Last Update Posted:	January 9, 2018
Last Verified:	January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No
Product Manufactured in and Exported from the U.S.:		No

Keywords provided by VA Office of Research and Development:

lung cancer; radiation pneumonitis; mitigation; enalapril; placebo

Additional relevant MeSH terms:

Pneumonia; Radiation Pneumonitis; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Lung Diseases, Interstitial; Lung Injury; Radiation Injuries	Wounds and Injuries; Enalapril; Enalaprilat; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents