Mitigation of Radiation Pneumonitis and Fibrosis - Full Text View

Purpose

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	Intervention	Phase
Lung Cancer Radiation Pneumonitis	Drug: Enalapril Drug: placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Care Provider) Primary Purpose: Prevention
Official Title:	Mitigation of Radiation Pneumonitis and Fibrosis

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Lung Cancer Pneumonia

Drug Information available for: Enalapril Enalapril maleate Enalaprilat

U.S. FDA Resources

Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:

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:

Radiation pneumonitis [ Time Frame: one year ]
The occurrence and grade of radiation pneumonitis by radiographic criteria, using CT scanning
Radiation fibrosis [ Time Frame: one year ]
The occurrence and grade of radiation fibrosis by radiographic criteria, using CT scanning
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.


Estimated Enrollment:	200
Actual Study Start Date:	November 1, 2013
Estimated Study Completion Date:	January 31, 2020
Estimated Primary Completion Date:	January 31, 2020 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Show Detailed Description

Eligibility


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01754909

Contacts


Contact: Eric P Cohen, MD	(410) 605-7182	Eric.Cohen@va.gov
Contact: Joseph E Berman, PT MHS	(414) 384-2000 ext 42408	joe.berman@va.gov

Locations


United States, Maryland
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Eric P Cohen, MD (410) 605-7182 Eric.Cohen@va.gov
Contact: Carly Goldstein, BA (410) 605-7000 carly.goldstein@va.gov
Principal Investigator: Eric Phin Cohen, MD
United States, Michigan
VA Ann Arbor Healthcare System, Ann Arbor, MI	Recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Michelle Mierzwa, MD 734-845-3713 michelle.mierzwa2@va.gov
United States, Wisconsin
Clement J. Zablocki VA Medical Center, Milwaukee, WI	Recruiting
Milwaukee, Wisconsin, United States, 53295-1000
Contact: Joseph Berman, PT 414-384-2000 ext 42408 joe.berman@va.gov

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

Publications:

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 )
Study First Received:	November 29, 2012
Last Updated:	August 4, 2017
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

ClinicalTrials.gov processed this record on September 20, 2017