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

Primary Purpose

Dyspnea, Non-small Cell Lung Cancer, Small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
lisinopril
placebo
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Dyspnea

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic
  • University of Nebraska Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (lisinopril)

Arm II (placebo)

Arm Description

Beginning within 7 days of beginning radiation therapy, patients receive lisinopril PO QD on days 1-7.

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

Outcomes

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
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

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).
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.
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.
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.

Full Information

First Posted
June 15, 2013
Last Updated
December 23, 2019
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01880528
Brief Title
Lisinopril in Reducing Shortness of Breath 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 Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
May 31, 2013 (Actual)
Primary Completion Date
June 5, 2013 (Actual)
Study Completion Date
January 29, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dyspnea, Non-small Cell Lung Cancer, Small Cell Lung Cancer

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (lisinopril)
Arm Type
Experimental
Arm Description
Beginning within 7 days of beginning radiation therapy, patients receive lisinopril PO QD on days 1-7.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Beginning within 7 days of beginning radiation therapy, patients receive placebo PO QD on days 1-7.
Intervention Type
Drug
Intervention Name(s)
lisinopril
Other Intervention Name(s)
Prinivil, Zestril
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Up to 3 months post-radiation therapy
Secondary Outcome Measure Information:
Title
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)
Description
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).
Time Frame
Up to 3 months post-radiation therapy
Title
Experience Shortness of Breath During Exercise as Measured Using Item #3 on the Symptom Experience Questionnaire (SEQ) at Week 4
Description
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.
Time Frame
At Week 4
Title
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
Description
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.
Time Frame
At Week 4
Title
Total LCSS Score as Measure by the Lung Cancer Symptom Scale (LCSS) at Week 4
Description
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.
Time Frame
At Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Miller, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States

12. IPD Sharing Statement

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

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