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

Condition(s) targeted: Dyspnea; Non-small Cell Lung Cancer; Small Cell Lung Cancer

Intervention: lisinopril (Drug); placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
Robert Miller, M.D., Study Chair, Affiliation: Mayo Clinic

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Primary outcome: 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

Secondary outcome:

Incidence of adverse events as measured using the NCI CTCAE version 4.0

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)

Incidence of acute respiratory distress (dyspnea), measured using the maximum score, at any time, of the shortness of breath question on the LCSS

Patient-level symptoms as measured using the Symptom Experience Questionnaire (SEQ)

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Mayo Clinic in Arizona, Scottsdale, Arizona 85259, United States; Recruiting
Mayo Clinic Clinical Trials Office, Phone: 855-776-0015
Steven E. Schild, M.D., Principal Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Mayo Clinic Clinical Trials Office, Phone: 855-776-0015
Robert C. Miller, M.D., Principal Investigator

University of Nebraska Medical Center, Omaha, Nebraska 68198, United States; Recruiting
Apar K. Ganti, Phone: 402-559-6520, Email: aganti@unmc.edu
Apar K. Ganti, Principal Investigator

Starting date: May 2013
Last updated: March 23, 2015