Dyspnea, Non-small Cell Lung Cancer, Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGlisinopril
Given PO
DRUGplacebo
Given PO
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Lisinopril) Beginning within 7 days of beginning radiation therapy, patients receive lisinopril PO QD. | 11 |
| Arm II (Placebo) Beginning within 7 days of beginning radiation therapy, patients receive placebo PO QD. | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 1 | 1 |
Baseline characteristics
| Characteristic | Arm I (Lisinopril) | Arm II (Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 62.0 years | 62.0 years | 62.0 years |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 |
| other Total, other adverse events | 11 / 12 | 10 / 10 |
| serious Total, serious adverse events | 4 / 12 | 1 / 10 |
Outcome results
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.
Time frame: Up to 3 months post-radiation therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Lisinopril) | 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 | 0 percentage of patients |
| Arm II (Placebo) | 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 | 0 percentage of patients |
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).
Time frame: Up to 3 months post-radiation therapy
Population: Patients who completed the LCSS Item #4 at any time during the study are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Lisinopril) | 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) | 77.5 score on a scale | Standard Deviation 23.8 |
| Arm II (Placebo) | 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) | 42.0 score on a scale | Standard Deviation 27.8 |
p-value: 0.006Kruskal-Wallis
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.
Time frame: At Week 4
Population: Patients who completed Item #3 on the SEQ at week 4 are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Lisinopril) | Experience Shortness of Breath During Exercise as Measured Using Item #3 on the Symptom Experience Questionnaire (SEQ) at Week 4 | 100 score on a scale | Standard Deviation 0 |
| Arm II (Placebo) | Experience Shortness of Breath During Exercise as Measured Using Item #3 on the Symptom Experience Questionnaire (SEQ) at Week 4 | 68.6 score on a scale | Standard Deviation 27.9 |
p-value: 0.0337Kruskal-Wallis
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.
Time frame: At Week 4
Population: Patients who completed item #5 on the EORTC-QLQ-LC13 at week 4 are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Lisinopril) | 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 | 83.3 score on a scale | Standard Deviation 17.8 |
| Arm II (Placebo) | 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 | 51.9 score on a scale | Standard Deviation 33.8 |
p-value: 0.0427Kruskal-Wallis
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.
Time frame: At Week 4
Population: Patients who completed the LCSS at week 4 are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Lisinopril) | Total LCSS Score as Measure by the Lung Cancer Symptom Scale (LCSS) at Week 4 | 83.8 score on a scale | Standard Deviation 11.2 |
| Arm II (Placebo) | Total LCSS Score as Measure by the Lung Cancer Symptom Scale (LCSS) at Week 4 | 66.5 score on a scale | Standard Deviation 17 |
p-value: 0.0237Kruskal-Wallis