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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01880528
• Other study ID #: MC1221
• Secondary ID: NCI-2013-0113912
• Status: Completed
• Phase: Phase 2
• Start date: May 31, 2013
• Est. completion date: January 29, 2019

Study information

• Verified date: December 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: January 29, 2019
• Est. primary completion date: June 5, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dyspnea
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• lisinopril
Given PO
• placebo
Given PO

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to 3 months post-radiation therapy
Secondary	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)	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).	Up to 3 months post-radiation therapy
Secondary	Experience Shortness of Breath During Exercise as Measured Using Item #3 on the Symptom Experience Questionnaire (SEQ) 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.	At Week 4
Secondary	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	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.	At Week 4
Secondary	Total LCSS Score as Measure by the Lung Cancer Symptom Scale (LCSS) 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.	At Week 4