Dyspnea, Malignant Neoplasm
Conditions
Brief summary
This phase II trial studies how well dexamethasone works in controlling dyspnea in patients with cancer. Dexamethasone may help control dyspnea (shortness of breath) and improve lung function and quality of life in cancer patients.
Detailed description
PRIMARY OBJECTIVES: I. Compare the intensity of dyspnea (numeric rating scale \[NRS\]) in the dexamethasone arm with that in the placebo arm at week 1. SECONDARY OBJECTIVES: I. Compare the effects of dexamethasone with those of placebo in terms of personalized dyspnea response (based on a personalized dyspnea goal), unpleasantness of dyspnea, other symptoms, health-related quality of life, respiratory physiologic function, and adverse effects at week 1 and week 2, as well as the intensity of dyspnea at week 2. II. Identify predictive markers of dyspnea response to dexamethasone. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive dexamethasone orally (PO) twice daily (BID) on days 1-28 in the absence of disease progression or unacceptable toxicity. GROUP II: Patients receive placebo PO BID on days 1-14 and dexamethasone PO BID on days 15-28 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at days 28 and 42.
Interventions
DRUGDexamethasone
Given PO
OTHERPlacebo
Given PO
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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
* Diagnosis of cancer. * Dyspnea with an average intensity \>= 4 on the dyspnea NRS (range 0-10) over the past week. * Radiologic suspicion of thoracic involvement, such as primary or metastatic lung cancer, lymphangitic carcinomatosis, airway infiltration, lymphadenopathy, pleural or chest wall invasion. * Seen at an outpatient clinic at MD Anderson Cancer Center or Lyndon B. Johnson (LBJ) Hospital General Oncology Clinic. * Able to communicate in English or Spanish. * Karnofsky performance status \>= 30%.
Exclusion criteria
* Delirium (i.e., score \> 13 on the Memorial Delirium Assessment Scale; range 1-30). * Oxygen saturation \< 90% despite supplemental oxygen \> 6 L/minute. * Previous allergic reactions to dexamethasone. * Diagnosis of diabetes mellitus uncontrolled with oral hypoglycemic agents or insulin. * Postsurgical open wound that has not healed at the time of enrollment. * Any infection requiring antibiotics at the time of study enrollment. * Major surgery within the past 2 weeks. * Megestrol use at the time of study enrollment. * Neutropenia (absolute neutrophil count \< 1.0 x 10\^9/L) at the time of study enrollment (bloodwork is not required if patient did not have chemotherapy within past 2 weeks). * Currently receiving or expected to start cytotoxic chemotherapy or immunotherapy within 1 week of study enrollment and additional dexamethasone cannot be used concurrently as per attending oncologist. * Severe anemia (hemoglobin \< 8 g/L) not corrected prior to study enrollment (bloodwork is not required if patient did not have chemotherapy within past 2 weeks). * Chronic obstructive pulmonary disease (COPD) exacerbation at the time of study enrollment. * Heart failure exacerbation at the time of study enrollment. * Expected to undergo therapeutic thoracentesis in the next 2 weeks. * High anxiety score (\>= 15/21) on the Hospital Anxiety and Depression Scale (HADS). * Chronic systemic corticosteroid use (\> 14 days) at the time of study enrollment. * Any expected corticosteroid use during study enrollment at higher doses than will be used in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Intensity | Baseline and Day 7 | The average dyspnea intensity over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea scores between Baseline and Day 7 were measured. Linear model analysis was used for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Intensity | Baseline and Day 14 | The average dyspnea intensity over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea scores between Baseline and Day 14 were measured. Linear model analysis was used for analysis. |
| Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Unpleasantness | Baseline and Day 7 | The average dyspnea unpleasantness over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea unpleasantness scores between Baseline and Day 7 were measured. Linear model analysis was used for analysis. |
| Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 7 | Baseline and Day 7 | ESAS (Edmonton Symptom Assessment Scale) is a validated scale ranging from 0 (not at all) to 10 (very much) used to assess 10 symptoms commonly experienced by cancer patients during the previous 24 hours: pain, fatigue, nausea, depression, anxiety, drowsiness, dyspnea, anorexia, sleep and feeling of well being. The change in ESAS fatigue score between Baseline and Day 7 were measured. Total ESAS fatigue score ranged from 0-10, with a higher score indicating higher fatigue. Linear model analysis was used for analysis. |
| Change in European Organization for Research and Treatment of Cancer-Quality of Life (EORTC QLQ-C30) Dyspnea Score Between Baseline and Day 7 | Baseline and Day 7 | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a well-validated quality-of-life assessment for patients with cancer, consisting of 30 questions that encompass three symptom scales (pain, fatigue, and nausea/vomiting) and six questions about single symptoms, as well as five functional scales (physical, cognitive, role, emotional, and social) and one scale assessing global health status/quality of life. Each single symptoms have four response categories (1=not at all, and 4=very much). The change in EORTC fatigue score between Baseline and Day 7 were measured. Total scores using a complex scoring procedures ranges from 0 to 100 with a higher scores indicating higher fatigue. Linear model analysis was used for analysis. |
| Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Unpleasantness | Baseline and Day 14 | The average dyspnea unpleasantness over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea unpleasantness scores between Baseline and Day 14 were measured. Linear model analysis was used for analysis. |
| Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 14 | Baseline and Day 14 | ESAS (Edmonton Symptom Assessment Scale) is a validated scale ranging from 0 (not at all) to 10 (very much) used to assess 10 symptoms commonly experienced by cancer patients during the previous 24 hours: pain, fatigue, nausea, depression, anxiety, drowsiness, dyspnea, anorexia, sleep and feeling of well being. The change in ESAS fatigue score between Baseline and Day 14 were measured. Total ESAS fatigue score ranged from 0-10, with a higher score indicating higher fatigue. Linear model analysis was used for analysis. |
| Change in European Organization for Research and Treatment of Cancer Quality of Life (EORTC) Dyspnea Score Between Baseline and Day 14 | Baseline and Day 14 | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a well-validated quality-of-life assessment for patients with cancer, consisting of 30 questions that encompass three symptom scales (pain, fatigue, and nausea/vomiting) and six questions about single symptoms, as well as five functional scales (physical, cognitive, role, emotional, and social) and one scale assessing global health status/quality of life. Each single symptoms have four response categories (1=not at all, and 4=very much). The change in EORTC fatigue score between Baseline and Day 14 were measured. Total scores using a complex scoring procedures ranges from 0 to 100 with a higher scores indicating higher fatigue. Linear model analysis was used for analysis. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid Hui
M.D. Anderson Cancer Center
Participant flow
Recruitment details
Ambulatory patients with cancer age ≥18, average dyspnea intensity over the past week ≥4/10 in a 0-10 point numeric rating scale, Karnofsky performance status ≥30% and ability to communicate in English or Spanish were selected from MD Anderson Cancer Center and Lyndon B. Johnson General Hospital, Houston, Texas, United States.
Pre-assignment details
A total of 135 participants were enrolled but 128 were randomized. 7 participants were not randomized for various reasons.
Participants by arm
| Arm | Count |
|---|---|
| Dexamethasone Participants were given 2 capsules (4mg each) by mouth twice daily (day1-day7), then 1 capsule twice daily for the next 7 days (day 8-day 14). | 85 |
| Placebo Placebo capsules were given 2 capsules (4mg each) by mouth twice daily (day1-day7), then 1 capsule twice daily for the next 7 days (day 8-day 14). | 43 |
| Total | 128 |
Baseline characteristics
| Characteristic | Placebo | Total | Dexamethasone |
|---|---|---|---|
| Age, Continuous | 63 years | 65 years | 66 years |
| Cancer Stage Stage III | 4 Participants | 21 Participants | 17 Participants |
| Cancer Stage Stage I-II | 15 Participants | 33 Participants | 18 Participants |
| Cancer Stage Stage IV | 24 Participants | 74 Participants | 50 Participants |
| Cancer Type Breast | 2 Participants | 7 Participants | 5 Participants |
| Cancer Type Gastrointestinal | 7 Participants | 13 Participants | 6 Participants |
| Cancer Type Genitourinary | 4 Participants | 6 Participants | 2 Participants |
| Cancer Type Other | 3 Participants | 10 Participants | 7 Participants |
| Cancer Type Respiratory | 27 Participants | 92 Participants | 65 Participants |
| Comorbidity Asthma | 5 Participants | 11 Participants | 6 Participants |
| Comorbidity Bronchiectasis | 1 Participants | 2 Participants | 1 Participants |
| Comorbidity COPD | 12 Participants | 44 Participants | 32 Participants |
| Comorbidity Heart Failure | 3 Participants | 8 Participants | 5 Participants |
| Comorbidity Other | 1 Participants | 6 Participants | 5 Participants |
| Comorbidity Pulmonary Embolism | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 21 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 107 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 20 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 34 Participants | 105 Participants | 71 Participants |
| Region of Enrollment United States | 43 participants | 128 participants | 85 participants |
| Sex: Female, Male Female | 24 Participants | 74 Participants | 50 Participants |
| Sex: Female, Male Male | 19 Participants | 54 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 85 | 0 / 43 |
| other Total, other adverse events | 32 / 85 | 7 / 43 |
| serious Total, serious adverse events | 24 / 85 | 3 / 43 |
Outcome results
Primary
Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Intensity
The average dyspnea intensity over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea scores between Baseline and Day 7 were measured. Linear model analysis was used for analysis.
Time frame: Baseline and Day 7
Population: The Dyspnea Average Intensity Numeric score was missing for 4 participants in the Dexamethasone Arm and 1 participant in the Placebo Arm.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dexamethasone | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Intensity | -1.6 score on a scale |
| Placebo | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Intensity | -1.6 score on a scale |
p-value: 0.4895% CI: [-0.8, 0.7]Linear Model
Secondary
Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Intensity
The average dyspnea intensity over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea scores between Baseline and Day 14 were measured. Linear model analysis was used for analysis.
Time frame: Baseline and Day 14
Population: Participants who were on the study at day 14 and received assessment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dexamethasone | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Intensity | -1.8 score on a scale |
| Placebo | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Intensity | -1.9 score on a scale |
p-value: >0.9995% CI: [-0.7, 1]Linear Model
Secondary
Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Unpleasantness
The average dyspnea unpleasantness over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea unpleasantness scores between Baseline and Day 14 were measured. Linear model analysis was used for analysis.
Time frame: Baseline and Day 14
Population: The Dyspnea Average Unpleasantness score was missing for 1 participant in the Placebo Arm. Participants who were on the study at day 14 and received assessment in the Dexamethasone Arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexamethasone | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Unpleasantness | -1.7 score on a scale |
| Placebo | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 14 Average Unpleasantness | -2.3 score on a scale |
p-value: 0.9395% CI: [-0.6, 1.8]Linear Model
Secondary
Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Unpleasantness
The average dyspnea unpleasantness over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10. The total score ranged from 0-10 where higher scores indicate worse dyspnea. The change in Dyspnea unpleasantness scores between Baseline and Day 7 were measured. Linear model analysis was used for analysis.
Time frame: Baseline and Day 7
Population: The Dyspnea Average Unpleasantness Numeric score was missing for 4 participants in the Dexamethasone Arm and 2 participant in the Placebo Arm.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dexamethasone | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Unpleasantness | -1.8 score on a scale |
| Placebo | Change in Dyspnea Numeric Score Over the Past 24 Hours for Baseline and Day 7 Average Unpleasantness | -2.2 score on a scale |
p-value: 0.9795% CI: [-0.7, 1.6]Linear Model
Secondary
Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 14
ESAS (Edmonton Symptom Assessment Scale) is a validated scale ranging from 0 (not at all) to 10 (very much) used to assess 10 symptoms commonly experienced by cancer patients during the previous 24 hours: pain, fatigue, nausea, depression, anxiety, drowsiness, dyspnea, anorexia, sleep and feeling of well being. The change in ESAS fatigue score between Baseline and Day 14 were measured. Total ESAS fatigue score ranged from 0-10, with a higher score indicating higher fatigue. Linear model analysis was used for analysis.
Time frame: Baseline and Day 14
Population: The ESAS Dyspnea score was missing for 3 participants in the Dexamethasone Arm and 2 participant in the Placebo Arm. Participants who were on the study at day 14 and received assessment in the Dexamethasone Arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexamethasone | Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 14 | -2 score on a scale |
| Placebo | Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 14 | -1 score on a scale |
p-value: 0.8295% CI: [-0.9, 1.1]Linear Model
Secondary
Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 7
ESAS (Edmonton Symptom Assessment Scale) is a validated scale ranging from 0 (not at all) to 10 (very much) used to assess 10 symptoms commonly experienced by cancer patients during the previous 24 hours: pain, fatigue, nausea, depression, anxiety, drowsiness, dyspnea, anorexia, sleep and feeling of well being. The change in ESAS fatigue score between Baseline and Day 7 were measured. Total ESAS fatigue score ranged from 0-10, with a higher score indicating higher fatigue. Linear model analysis was used for analysis.
Time frame: Baseline and Day 7
Population: The ESAS Dyspnea Numeric score was missing for 3 participants in the Dexamethasone Arm and 2 participant in the Placebo Arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexamethasone | Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 7 | -1 score on a scale |
| Placebo | Change in Edmonton Symptom Assessment Scale (ESAS) Dyspnea Score Between Baseline and Day 7 | -1.5 score on a scale |
p-value: 0.7895% CI: [-0.8, 1]Linear Model
Secondary
Change in European Organization for Research and Treatment of Cancer Quality of Life (EORTC) Dyspnea Score Between Baseline and Day 14
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a well-validated quality-of-life assessment for patients with cancer, consisting of 30 questions that encompass three symptom scales (pain, fatigue, and nausea/vomiting) and six questions about single symptoms, as well as five functional scales (physical, cognitive, role, emotional, and social) and one scale assessing global health status/quality of life. Each single symptoms have four response categories (1=not at all, and 4=very much). The change in EORTC fatigue score between Baseline and Day 14 were measured. Total scores using a complex scoring procedures ranges from 0 to 100 with a higher scores indicating higher fatigue. Linear model analysis was used for analysis.
Time frame: Baseline and Day 14
Population: The EORTC Dyspnea score was missing for 2 participants in the Dexamethasone Arm and 3 participant in the Placebo Arm. Participants who were on the study at day 14 and received assessment in the Dexamethasone Arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexamethasone | Change in European Organization for Research and Treatment of Cancer Quality of Life (EORTC) Dyspnea Score Between Baseline and Day 14 | -33.3 score on a scale |
| Placebo | Change in European Organization for Research and Treatment of Cancer Quality of Life (EORTC) Dyspnea Score Between Baseline and Day 14 | -33.3 score on a scale |
p-value: 0.3895% CI: [-17.9, 6.9]Linear Model
Secondary
Change in European Organization for Research and Treatment of Cancer-Quality of Life (EORTC QLQ-C30) Dyspnea Score Between Baseline and Day 7
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a well-validated quality-of-life assessment for patients with cancer, consisting of 30 questions that encompass three symptom scales (pain, fatigue, and nausea/vomiting) and six questions about single symptoms, as well as five functional scales (physical, cognitive, role, emotional, and social) and one scale assessing global health status/quality of life. Each single symptoms have four response categories (1=not at all, and 4=very much). The change in EORTC fatigue score between Baseline and Day 7 were measured. Total scores using a complex scoring procedures ranges from 0 to 100 with a higher scores indicating higher fatigue. Linear model analysis was used for analysis.
Time frame: Baseline and Day 7
Population: The EORTC QLQ-C30 Dyspnea score was missing for 4 participants in the Dexamethasone Arm and 2 participant in the Placebo Arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexamethasone | Change in European Organization for Research and Treatment of Cancer-Quality of Life (EORTC QLQ-C30) Dyspnea Score Between Baseline and Day 7 | -33.3 score on a scale |
| Placebo | Change in European Organization for Research and Treatment of Cancer-Quality of Life (EORTC QLQ-C30) Dyspnea Score Between Baseline and Day 7 | -33.3 score on a scale |
p-value: 0.9395% CI: [-10.6, 9.6]Linear Model