Captopril in Treating Patients With Non-Small Cell Lung Cancer or Limited-Stage Small Cell Lung Cancer That Has Been Previously Treated With Radiation Therapy With or Without Chemotherapy

Lung Cancer Clinical Trial

Official title:

A Phase II Randomized Trial With Captopril In Patients Who Have Received Radiation Therapy +/- Chemotherapy For Stage II-IIIB Non-Small Cell Lung Cancer, Stage I Central Non-Small Cell Lung Cancer, Or Limited-Stage Small-Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00077064
• Other study ID #: RTOG-0123
• Secondary ID: CDR0000315569RTO
• Status: Terminated
• Phase: Phase 2
• First received: February 10, 2004
• Last updated: February 6, 2018
• Start date: June 2003
• Est. completion date: December 2016

Study information

• Verified date: February 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Captopril is a drug that may be able to decrease side effects caused by radiation therapy, and may improve the quality of life of patients with non-small cell lung cancer or limited-stage small cell lung cancer.

PURPOSE: This randomized phase II trial is studying how well captopril works in decreasing side effects and improving the quality of life in patients who have received radiation therapy with or without chemotherapy for stage I, stage II, or stage IIIB non-small cell lung cancer or limited-stage small cell lung cancer.

Description:

OBJECTIVES:

• Determine the effect of captopril on the incidence of pulmonary damage at 12 months after radiotherapy with or without chemotherapy in patients with stage II-IIIB non-small cell lung cancer, stage I central non-small cell lung cancer, or limited stage small cell lung cancer.

• Compare the quality of life of patients treated with captopril vs patients who undergo post-radiotherapy observation only.

• Determine the persistence of captopril's effect on pulmonary toxicity in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, total lung irradiated (< 25% vs 25-37% vs more than 37%), prior surgery (yes vs no), and prior chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral captopril 3 times daily for 1 year in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo observation only for 1 year. Quality of life is assessed at baseline and at months 3, 6, 12, and 18.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 205 patients will be accrued for this study within 18 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 81
• Est. completion date: December 2016
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• One of the following histologically or cytologically confirmed diagnoses:

• Stage II-IIIB non-small cell lung cancer (NSCLC)

• Stage I central NSCLC

• No peripheral coin lesions

• Limited stage small cell lung cancer

• Nonmetastatic disease that is receiving radiotherapy and the target is confined to a single radiotherapy treatment area

• Planning to receive radiotherapy

• At least 45 Gy to be delivered to the target volume

• More than 25% of total lung volume to receive > 20 Gy if receiving radiotherapy alone

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Hematopoietic

• Absolute granulocyte count greater than 1,000/mm^3

• Platelet count greater than 75,000/mm^3

• Hemoglobin greater than 9.0 g/dL (transfusion allowed)

Hepatic

• Bilirubin less than 1.5 mg/dL

• Serum glutamate oxaloacetate transaminase (SGOT) less than 2 times normal

Renal

• Blood urea nitrogen (BUN) less than 25 mg/dL

• Creatinine less than 1.6 mg/dL

• Urine protein less than 10 mg/dL

• Urine glucose negative

Cardiovascular

• Systolic blood pressure greater than 110 mm Hg

• Diastolic blood pressure greater than 60 mm Hg

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Sodium normal

• Potassium normal

• No collagen vascular disease (e.g., lupus or scleroderma)

• Rheumatoid arthritis allowed

• No known hypersensitivity to ACE inhibitors

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Induction or concurrent chemotherapy allowed either during radiotherapy or during therapy with captopril

• No concurrent methotrexate

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Prior pulmonary lobectomy or segmentectomy allowed

• No prior pneumonectomy

Other

• No concurrent angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists for hypertension or congestive heart failure

• No concurrent lithium

• No concurrent procainamide

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Fibrosis
• Lung Cancer
• Lung Neoplasms
• Pulmonary Complications
• Radiation Fibrosis
• Radiation Pneumonitis
• Small Cell Lung Carcinoma

Intervention

Drug:
• captopril
Captopril 12.5 mg t.i.d. for first two weeks, increased to 25 mg t.i.d. for the second two weeks of therapy. Thereafter, the dose will be increased to 50 mg t.i.d. for the remainder of the one-year of therapy (52 total weeks of drug administration).

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	Saint John's Cancer Center at Saint John's Medical Center	Anderson	Indiana
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	Cancer Treatment Center for Southern Kentucky	Bowling Green	Kentucky
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	New York Methodist Hospital	Brooklyn	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Great Lakes Cancer Institute at McLaren Regional Medical Center	Flint	Michigan
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Fremont Memorial Hospital	Fremont	Ohio
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Central Maine Comprehensive Cancer Center at Central Maine Medical Center	Lewiston	Maine
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Lima Memorial Hospital	Lima	Ohio
United States	Veterans Affairs Medical Center - Long Beach	Long Beach	California
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin
United States	Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Trinity CancerCare Center	Minot	North Dakota
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York
United States	Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center	Pomona	California
United States	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin
United States	Cancer Centers of North Carolina - Raleigh	Raleigh	North Carolina
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Firelands Regional Medical Center	Sandusky	Ohio
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Mercy Medical Center	Springfield	Ohio
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	General Robert Huyser Cancer Center at David Grant Medical Center	Travis Air Force Base	California
United States	Fulton County Health Center	Wauseon	Ohio
United States	West Allis Memorial Hospital	West Allis	Wisconsin
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Wilmed Radiation Oncology Services	Wilson	North Carolina
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Therapy-induced Lung Toxicity	Incidence of Grade 2+ radiation-induced pulmonary toxicity within 1 year after completion of radiation. Assuming that the incidence of pulmonary toxicity would be 50%, based on Fisher's exact test with a one-sided significance level of 0.05,168 randomized patients would be required to have 80% statistical power to detect a 40% relative reduction (from 50% to 30%) in the incidence of pulmonary toxicity while receiving captopril. Assuming that 15% of cases would not continue to the randomization stage and 5% of patients would be found ineligible, the target sample size was 205 patients. Given the actual sample size, power would be 25% and therefore p-values were not reported.	Once all patients have been followed for at least 12 months
Secondary	Correlation of Lung Toxicities With Biochemical Markers	Biomarker data will not be generated from these tissue specimens, therefore this analysis will not take place.	Once all patients have been followed for at least 12 months
Secondary	Correlation of Quality of Life With Late Effects as Measured by European Organization for Research and Treatment of Cancer (EORTC) C-30 or EORTC Lung Cancer Module (LC-13)	Only 2 patients have the required data- only 1.2% of the planned enrollment and 2.5% of the actual enrollment- which is extremely problematic as this data cannot be generalized, leads to selection bias, and is not representative of the patient population. Therefore the analysis was not conducted.	Baseline to 18 months post treatment
Secondary	Persistence of Pulmonary Toxicity at 2 Years After Completion of Study Treatment	Patients who experienced a Grade 2+ radiation-induced pulmonary toxicity within 1 year after completion of radiation were assessed to determine if the toxicity persisted for 2 years.	2 years from completion of study treatment