Lisinopril in Reducing Shortness of Breath Caused by Radiation Therapy in Patients With Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert C. Miller, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01880528
First received: June 15, 2013
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

This pilot clinical trial studies lisinopril in reducing shortness of breath caused by radiation therapy in patients with lung cancer. Lisinopril may decrease the side effects caused by radiation therapy in patients with lung cancer.


Condition Intervention
Dyspnea
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Drug: lisinopril
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: A Double-Blind Pilot Study to Measure the Effect of Lisinopril vs. Placebo on Pulmonary Distress in Patients Receiving External Beam Radiotherapy to the Lung

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Incidence of grade 3 or higher hypotension, acute kidney injury, allergic reaction, or anaphylaxis, as measured using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 3 months post-radiation therapy ] [ Designated as safety issue: Yes ]
    Descriptive statistics of frequency (percentage) will be used to summarize adverse event (AE) incidence and severity in the lisinopril and placebo arms separately. Should incidence rates differ between the treatment arms, the Chi-square test may be utilized in an exploratory fashion to further characterize the differences. The difference between the two arms (point estimate and 95% confidence interval) will be reported.


Secondary Outcome Measures:
  • Incidence of adverse events as measured using the NCI CTCAE version 4.0 [ Time Frame: Up to 3 months post-radiation therapy ] [ Designated as safety issue: Yes ]
    An entire AE profile for both treatment arms will be compiled using descriptive statistics of frequency (percentage). Should incidence rates differ between the treatment arms, the Fisher's exact test or Chi-square test may be utilized in an exploratory fashion to further characterize the differences. The difference between the two arms (point estimate and 95% confidence interval) will be reported.

  • Quality of life, assessed using lung cancer symptom scale (LCSS), Functional Assessment of Cancer Treatment Lung Cancer (FACT-L), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer (EORTC-QLQ-LC13) [ Time Frame: Up to 3 months post-radiation therapy ] [ Designated as safety issue: No ]
    The LCSS, FACT-L, and EORTC-QLQ-LC13 will be scored according to their respective scoring algorithms. All continuous QOL data will be converted to 0-100 point scales where 100 is best QOL, for comparability. Descriptive statistics (means, standard deviations, and 95% confidence intervals) will be compiled for maximum scores over time, actual scores at each time point, and change from baseline scores. Frequencies (percentages) will be utilized to compile individual item responses.

  • Incidence of acute respiratory distress (dyspnea), measured using the maximum score, at any time, of the shortness of breath question on the LCSS [ Time Frame: Up to 3 months post-radiation therapy ] [ Designated as safety issue: No ]
    Descriptive statistics (means, standard deviations, and 95% confidence intervals) will be compiled in the lisinopril and placebo arms separately. Statistical tests (two-sample t-test or Wilcoxon rank-sum test) may be employed to determine differences, if any, occur between treatment arms. The difference between the two arms (point estimate and 95% confidence interval) will be reported.

  • Patient-level symptoms as measured using the Symptom Experience Questionnaire (SEQ) [ Time Frame: Up to 3 months post-radiation therapy ] [ Designated as safety issue: No ]
    Descriptive statistics (means, standard deviations, and 95% confidence intervals) will be utilized to summarize each individual SEQ response within each treatment arm separately. Statistical tests (two-sample t-test or Wilcoxon rank-sum test) may be employed to determine differences, if any, occur between treatment arms. The difference between the two arms (point estimate and 95% confidence interval) will be reported.


Estimated Enrollment: 50
Study Start Date: May 2013
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (lisinopril)
Beginning within 7 days of beginning radiation therapy, patients receive lisinopril PO QD on days 1-7.
Drug: lisinopril
Given PO
Other Names:
  • Prinivil
  • Zestril
Placebo Comparator: Arm II (placebo)
Beginning within 7 days of beginning radiation therapy, patients receive placebo PO QD on days 1-7.
Drug: placebo
Given PO
Other Name: PLCB

Detailed Description:

PRIMARY OBJECTIVES:

I. To explore the adverse event profile of lisinopril, during and after external beam radiation therapy (RT) to the lung.

SECONDARY OBJECTIVES:

I. To explore the level of patient-reported acute respiratory distress (dyspnea) during and after external beam RT.

II. To explore the level of patient-reported symptoms during and after external beam RT.

III. To explore the impact of lisinopril treatment on patient quality of life (QOL) during and after external beam RT.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Beginning within 7 days of beginning radiation therapy, patients receive lisinopril orally (PO) once daily (QD) on days 1-7.

ARM II: Beginning within 7 days of beginning radiation therapy, patients receive placebo PO QD on days 1-7.

In both arms, treatment repeats every 7 days for until 3 months after completion of radiation therapy in the absence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological confirmation of small cell and non-small cell carcinoma of the lung receiving thoracic radiotherapy > 45 Gy, with volume of lung receiving 20 Gy or more (V20Gy) >= 20%
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin > 9.0 g/dL
  • Creatinine clearance >= 30 mL/min as calculated using actual body weight and Cockroft Gault formula
  • Initial physical exam with systolic blood pressure (BP) of > 100 mmHg and diastolic BP of > 60 mmHg
  • Potassium within institutional normal limits
  • Sodium within institutional normal limits
  • Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Other active malignancy =< 3 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment (e.g., maintenance or adjuvant chemotherapy or hormonal therapy) for their cancer
  • History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • History of prior radiation therapy treatment to the lungs or thorax
  • Existing contraindications to angiotensin-converting enzyme (ACE) inhibitors such as hypersensitivity to ACE inhibitors, bilateral renal artery stenosis, angioedema, or previously documented adverse drug reaction to ACE inhibitors
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Use of ACE inhibitors (including lisinopril) or ACE receptor blockers (ARB) of any kind =< 90 days prior to registration
  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: NCT01880528

Locations
United States, Arizona
Mayo Clinic Scottsdale-Phoenix Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Steven E. Schild, M.D.         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Robert C. Miller, M.D.         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Apar K. Ganti    402-559-6520    aganti@unmc.edu   
Principal Investigator: Apar K. Ganti         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Robert Miller, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Robert C. Miller, M.D., Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01880528     History of Changes
Other Study ID Numbers: MC1221, NCI-2013-01139, 12-008062, P30CA015083
Study First Received: June 15, 2013
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Dyspnea
Lung Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Signs and Symptoms
Lisinopril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014