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

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.

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