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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

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ClinicalTrials.gov Identifier: NCT00077064
Recruitment Status : Terminated (Due to unmet accrual/randomization goals)
First Posted : February 11, 2004
Results First Posted : March 8, 2018
Last Update Posted : March 8, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Brief 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.


Condition or disease Intervention/treatment Phase
Lung Cancer Pulmonary Complications Radiation Fibrosis Drug: captopril Phase 2

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  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
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
Study Start Date : June 2003
Actual Primary Completion Date : November 2008
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Captopril

Arm Intervention/treatment
No Intervention: Observation
Clinical observation
Experimental: Captopril
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).




Primary Outcome Measures :
  1. Incidence of Therapy-induced Lung Toxicity [ Time Frame: Once all patients have been followed for at least 12 months ]
    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.


Secondary Outcome Measures :
  1. Correlation of Lung Toxicities With Biochemical Markers [ Time Frame: Once all patients have been followed for at least 12 months ]
    Biomarker data will not be generated from these tissue specimens, therefore this analysis will not take place.

  2. 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) [ Time Frame: Baseline to 18 months post treatment ]
    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.

  3. Persistence of Pulmonary Toxicity at 2 Years After Completion of Study Treatment [ Time Frame: 2 years from 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00077064


  Show 87 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Study Chair: William Small, MD Robert H. Lurie Cancer Center

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00077064     History of Changes
Other Study ID Numbers: RTOG-0123
CDR0000315569
RTOG-L-0123
First Posted: February 11, 2004    Key Record Dates
Results First Posted: March 8, 2018
Last Update Posted: March 8, 2018
Last Verified: February 2018

Keywords provided by Radiation Therapy Oncology Group:
radiation fibrosis
pulmonary complications
limited stage small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage I non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Fibrosis
Small Cell Lung Carcinoma
Radiation Pneumonitis
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pathologic Processes
Lung Diseases, Interstitial
Lung Injury
Radiation Injuries
Wounds and Injuries
Captopril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents