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

Phase 2

Completed

Conditions: Non-small Cell Lung Cancer
Small Cell Lung Cancer
Dyspnea

Interventions: Drug: placebo
Drug: lisinopril

Registration Number: NCT01880528

Lead Sponsor: Mayo Clinic

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (placebo)	placebo	Beginning within 7 days of beginning radiation therapy, patients receive placebo PO QD on days 1-7.
Arm I (lisinopril)	lisinopril	Beginning within 7 days of beginning radiation therapy, patients receive lisinopril PO QD on days 1-7.

Primary Outcome Measures

Name	Time	Method
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	Up to 3 months post-radiation therapy	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. Descriptive statistics of frequency (percentage) will be used to summarize adverse event (AE) incidence and severity in the lisinopril and placebo arms separately.

Secondary Outcome Measures

Name	Time	Method
Acute Respiratory Distress (Dyspnea), Measured Using of the Maximum Score, at Any Time, of the Shortness of Breath Question (Item #4) on the LCSS (Worst Dyspnea Score)	Up to 3 months post-radiation therapy	Acute respiratory distress (dyspnea), measured using of the maximum score, at any time, of the shortness of breath question (Item #4 "How much shortness of breath do you have?") on the Lung Cancer Symptom Scale (LCSS) (Worst Dyspnea Score). The LCSS tool contains 6 major symptoms associated with lung malignancies and their effect on overall symptomatic distress, functional activities, and global quality of life (QOL). The item scale ranges from 0-10 (0 = None; 10 = As much as it could be) where the LCSS scoring algorithm is applied to convert to a 0-100 point scale where 100 is best quality of life (QOL), for comparability. Patient scores range from 0 to 100, where 100 was best QOL (i.e. less pulmonary distress).
Experience Shortness of Breath During Exercise as Measured Using Item #3 on the Symptom Experience Questionnaire (SEQ) at Week 4	At Week 4	Experience shortness of breath during exercise as measured using Item #3 ("Over the past week, did you experience shortness of breath when you exercise or exert yourself?") on the Symptom Experience Questionnaire (SEQ) at Baseline. The item scale ranges from 0-10 (0 = Not at all; 10 = As bad as it can be) where the SEQ scoring algorithm is applied to convert to a 0-100 point scale where 100 is best quality of life (QOL), for comparability.
Quality of Life (Dyspnea When Climbing Stairs) Assessed Using Item #5 of the European Organization for Research on the Treatment of Cancer Lung Cancer Module Survey (EORTC-QLQ-LC13) at Week 4	At Week 4	Dyspnea when climbing as measured using item #5 ("Were you short of breath when you climbed stairs?") of the EORTC-QLQ-LC13 at Week 4. The item scale ranges from 1-4 (1 = Not at all; 4 = Very Much) where the EORTC-QLQ-LC13 scoring algorithm is applied to convert to a 0-100 point scale where 100 is best quality of life (QOL), for comparability.
Total LCSS Score as Measure by the Lung Cancer Symptom Scale (LCSS) at Week 4	At Week 4	Total LCSS score as measured using the Lung Cancer Symptom Scale (LCSS) at Week 4. The item scale ranges from 0-10 (0 = None; 10 = As much as it could be) where the LCSS scoring algorithm is applied to convert to a 0-100 point scale where 100 is best quality of life (QOL), for comparability.

Trial Locations

Locations (3): University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States