Mitigation of Radiation Pneumonitis and Fibrosis

NCT01754909 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLIN-004-12S1I01CX000569-01A2
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Lung Cancer; Radiation Pneumonitis

Keywords

lung cancer; radiation pneumonitis; mitigation; enalapril; placebo

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Radiation Pneumonitis

  The clinical occurrence and grade of radiation pneumonitis, by National Cancer Institute Common Terminology Criteria Adverse Event grading ( NCI CTCAE)

  two years

Secondary Outcomes (2)

• Number of Participants With Radiation Pneumonitis by CT Scan

  six months

• Number of Participants With Radiation Fibrosis

  one year

Study Arms (2)

enalapril

ACTIVE COMPARATOR

Use of enalapril in subjects undergoing radiotherapy for lung cancer.

Drug: Enalapril

placebo

PLACEBO COMPARATOR

Use of placebo in subjects undergoing radiotherapy for lung cancer

Drug: placebo

Interventions

Enalapril DRUG

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

enalapril

placebo DRUG

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

placebo

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (3)

Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Baltimore, Maryland, 21201, United States

Location

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105, United States

Location

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, 53295-1000, United States

Location

Related Publications (2)

• 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.

  PMID: 22300564 RESULT

• 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.

  PMID: 28489488 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Radiation Pneumonitis

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Interstitial; Lung Injury; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr Eric Cohen
• Organization: Baltimore VAMC

eric.cohen@va.gov

410 605 7000

Study Officials

• Eric P Cohen, MD

  Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2012
• First Posted: December 21, 2012
• Study Start: November 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: October 8, 2019
• Results First Posted: October 1, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)