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

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

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.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer; Pulmonary Complications; Radiation Fibrosis
• Intervention / Treatment: Drug: captopril

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Arizona Oncology Services Foundation
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Long Beach, California, United States, 90822
      • Veterans Affairs Medical Center - Long Beach
    • Pomona, California, United States, 91767
      • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
    • Travis Air Force Base, California, United States, 94535-1800
      • General Robert Huyser Cancer Center at David Grant Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at UC Health Sciences Center
  • Florida
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Miami, Florida, United States, 33176
      • Baptist-South Miami Regional Cancer Program
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint John's Cancer Center at Saint John's Medical Center
    • Indianapolis, Indiana, United States, 46202
      • Methodist Cancer Center at Methodist Hospital
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Cancer Treatment Center for Southern Kentucky
    • Lexington, Kentucky, United States, 40503-9985
      • Central Baptist Hospital
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Comprehensive Cancer Center at Central Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Flint, Michigan, United States, 48532
      • Great Lakes Cancer Institute at McLaren Regional Medical Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Lambertville, Michigan, United States, 48144
      • Haematology-Oncology Associates of Ohio and Michigan, PC
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital - Monroe
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
  • New Jersey
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
    • Marlton, New Jersey, United States, 08053
      • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
    • Toms River, New Jersey, United States, 08755
      • J. Phillip Citta Regional Cancer Center at Community Medical Center
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Plattsburgh, New York, United States, 12901
      • Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Raleigh, North Carolina, United States, 27607
      • Rex Cancer Center at Rex Hospital
    • Raleigh, North Carolina, United States, 27607
      • Cancer Centers of North Carolina - Raleigh
    • Wilson, North Carolina, United States, 27893
      • Wilmed Radiation Oncology Services
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Cancercare Center
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Wood County Oncology Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center Cancer Care
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Fremont, Ohio, United States, 43420
      • Fremont Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Northwest Ohio Oncology Center
    • Maumee, Ohio, United States, 43537
      • St. Luke's Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic - Oregon
    • Sandusky, Ohio, United States, 44870
      • Firelands Regional Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Springfield, Ohio, United States, 45504
      • Mercy Medical Center
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43617
      • CCOP - Toledo Community Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Mount Carmel St. Ann's Cancer Center
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology, Incorporated
  • Wisconsin
    • Mequon, Wisconsin, United States, 53097
      • Columbia Saint Mary's Hospital - Ozaukee
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia-Saint Mary's Cancer Care Center
    • Milwaukee, Wisconsin, United States, 53215
      • Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at Wheaton Franciscan Healthcare
    • West Allis, Wisconsin, United States, 53227
      • West Allis Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observation; Clinical observation
Experimental: Captopril	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 10, 2004
• First Submitted That Met QC Criteria: February 10, 2004
• First Posted (Estimate): February 11, 2004

Study Record Updates

• Last Update Posted (Actual): March 8, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage I non-small cell lung cancer; stage II non-small cell lung cancer; limited stage small cell lung cancer; pulmonary complications; radiation fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Wounds and Injuries; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases, Interstitial; Lung Injury; Radiation Injuries; Fibrosis; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Radiation Pneumonitis; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Captopril
• Other Study ID Numbers: RTOG-0123; CDR0000315569; RTOG-L-0123