Clinical trial NCT01670097
Conditions: Advanced Cancers Hematologic Disorder Solid Tumors
Keywords: Advanced Cancers Hematologic Disorder Solid Tumors Dyspnea Difficulty breathing Shortness of breath Dexamethasone Decadron Placebo Sugar pill Questionnaires Surveys Spirometer Phone calls
Sponsor: M.D. Anderson Cancer Center
Start date: 2013-01-01; Completion date: 2021-01-26
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The goal of this clinical research study is to learn if dexamethasone can help reduce shortness of breath in cancer patients. Researchers also want to learn if it can help to improve lung function and quality of life. In this study, dexamethasone will be compared to a placebo.

Dexamethasone is commonly used for treatment of nausea, tiredness, and pain. It may help patients with shortness of breath.

A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.

Detailed description:
Baseline Tests:

If you are found to be eligible to take part in this study, you will have baseline tests after completing the screening questionnaires. The following tests and procedures will be performed:

* Information will be collected from your medical record about your age, sex, race, disease type, how well you are able to perform the normal activities of daily living, any drugs you are taking, and possible causes of shortness of breath.
* Your breathing rate will be measured.
* The amount of oxygen in your body will be measured using a machine that clips on your finger.
* You will blow into a device called a spirometer a few times to measure your lung function.
* You will be asked to answer 4 questionnaires. The first questionnaire asks you to rate your level of symptoms, such as pain, tiredness, sleep, appetite, depression, anxiety, and drowsiness. The second questionnaire asks about your sensation of breathing. The third questionnaire asks you to rate the intensity of your shortness of breath. The last questionnaire asks about your quality of life. These questionnaires should take a total of about 40 minutes to complete.

Study Groups:

You will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups:

* If you are in Group 1, you will receive dexamethasone.
* If you are in Group 2, you will receive a placebo for 7 days, then dexamethasone for 7 days.

You will have an equal chance of being assigned to either group. Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.

Study Drug/Placebo Administration:

After your baseline tests, you will be given a supply of either the study drug or the placebo to bring home.

Starting the next morning, you will take 2 dexamethasone or placebo capsules twice a day by mouth for 4 days. Then, you will take 1 tablet twice a day for 3 more days.

After the first 7 days, no matter which group you have been assigned to, you will only take 1 dexamethasone capsule twice a day for 7 more days

You should take the capsules around 8 o'clock in the morning and 4 o'clock in the afternoon. You should take the capsules with food and 8 ounces of water.

You will also receive a portable spirometer to test your lung function. You should blow into the machine 1 time a day.

Study Visits/Calls:

On Days 7 and 14, you will return to the clinic or be called by phone. You should bring your capsule boxes with you if you come to the clinic, or have them with you if you are called so the study staff can count the number of capsules. The following tests and procedures will be performed:

* You will be asked to complete the same 4 questionnaires you completed during your baseline tests.
* You will also be asked about any side effects you may be having and if you think the study drug is helping your shortness of breath.
* You will blow into a spirometer to measure your lung function.

During the 14 days you will be taking either the study drug or the placebo on the study, you will be called by phone 1 time each day to ask you about your level of shortness of breath and to remind you to take the capsules. These calls should last about 5 minutes.

Length of Study:

You may continue taking the study drug for up to 14 days, as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if intolerable side effects occur or if you are unable to follow study directions.

Your participation on the study will be over when you have completed the follow-up calls and visit.

This is an investigational study. Dexamethasone is FDA approved and commercially available for the treatment of pain, nausea and tiredness. Its use to help control shortness of breath is investigational.

Up to 40 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Arms: arm 1: Dexamethasone 8 mg (2 capsules of 4 mg) given orally twice a day for 4 days, then 4 mg given orally twice a day for 3 days. In the open label phase, patients assigned to either arm asked to take Dexamethasone 4 mg orally twice a day for 7 days. Patient to blow into spirometry machine 1 time a day to test lung function. Questionnaires completed at baseline and at day 7 and 14. It should take about 15 minutes to complete these questionnaires. Questionnaires completed at baseline and at day 7 and 14. It should take about 15 minutes to complete these questionnaires.

Participants randomized to either dexamethasone or placebo for 7 days in a blinded fashion; this will be followed by an open label phase in which patients in both arms would take dexamethasone for 7 days. arm 2: Two placebo capsules taken twice a day for 4 days, followed by one capsule twice a day for 3 days. Patient to blow into spirometry machine 1 time a day to test lung function. Questionnaires completed at baseline and at day 7 and 14. It should take about 15 minutes to complete these questionnaires. Questionnaires completed at baseline and at day 7 and 14. It should take about 15 minutes to complete these questionnaires.

Participants randomized to either dexamethasone or placebo for 7 days in a blinded fashion; this will be followed by an open label phase in which patients in both arms would take dexamethasone for 7 days.
Interventions: intervention 1: Dexamethasone intervention 2: Placebo intervention 3: Questionnaires intervention 4: Spirometer intervention 5: Phone Calls
Intervention descriptions: intervention 1: Group 1 Blinded Phase: 8 mg (2 capsules of 4 mg) given orally twice a day for 4 days, then 4 mg given orally twice a day for 3 days.

Open Label Phase Groups 1 and 2: 4 mg by mouth twice a day for 7 days. intervention 2: Group 2 Blinded Phase: Two capsules by mouth twice a day for 4 days, followed by one capsule twice a day for 3 days. intervention 3: Questionnaires completed at baseline and at day 7 and 14. It should take about 15 minutes to complete these questionnaires. intervention 4: Patient to blow into spirometry machine 1 time a day to test lung function. intervention 5: Patient called by phone 1 time each day to ask about level of shortness of breath and to remind patient to take capsules. These calls should last about 5 minutes.

Protocol documents:
Prot_SAP_000.pdf: 
Protocol Page
A Preliminary Study of Dexamethasone for Dyspnea in Cancer Patients
2012-0001
Core Protocol Information
Short Title 
Dexamethasone Dyspnea Study
Study Chair: 
David Hui
Additional Contact:
Julio A. Allo
Susan Frisbee-Hume
Vera J. DeLaCruz
Additional Memo Recipients:
Recipients List
OPR Recipients (for OPR use only)
OPR DSMB
Study Staff Recipients
None
Department:
Palliative Care and Rehabilitation Medicine
Phone:
713-792-6258
Unit:
1414
Full Title: 
A Preliminary Study of Dexamethasone for Dyspnea in Cancer 
Patients
Protocol Type:
Standard Protocol
Protocol Phase:
Phase II
Version Status:
Activated 12/02/2013
Version:
14
Document Status:
Saved as "Final"
Submitted by:
Vera J. DeLaCruz--11/5/2013 3:28:10 PM
OPR Action:
Accepted by:  Virginia M Gonzales -- 11/14/2013 2:18:01 PM
Which Committee will review this protocol?
 The Clinical Research Committee - (CRC)
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Protocol Body
1.0 Objectives
A. Objectives
A.1. Primary Objective. To determine the feasibility of conducting a randomized controlled trial (blinded phase) on dexamethasone in 
cancer patients with dyspnea.  Our working hypothesis is that at least 50% of patients will complete the dyspnea numeric rating scale (NRS) 
on day 7+/-2.
A.2. Objective #2. To compare the intensity of dyspnea (NRS), forced expiratory volume (FEV1) and quality of life in cancer patients 
between baseline and after 4 days of dexamethasone use. Our working hypothesis is that 4 days of dexamethasone will improve dyspnea, 
respiratory function and quality of life for cancer patients.
A.3. Objective #3. To compare the intensity of dyspnea (NRS, cancer dyspnea scale), FEV1, and quality of life in cancer patients between 
baseline and after 7 days of dexamethasone use. Our working hypothesis is that 7 days of dexamethasone will improve dyspnea, 
respiratory function and quality of life for cancer patients.
A.4. Objective #4. To compare the intensity of dyspnea (NRS, cancer dyspnea scale), FEV1, in cancer patients between the 
dexamethasone arm and the placebo arm at 4 and 7 days.  Our working hypothesis is that dexamethasone will improve dyspnea, and 
respiratory function for cancer patients compared to placebo.
A.5. Objective #5. To compare the intensity of dyspnea (NRS, cancer dyspnea scale), FEV1, and quality of life in cancer patients after 7 
days of dexamethasone between the dexamethasone arm (8mg BID for 4 days followed by 4mg BID for 3 days) and the placebo arm (4mg 
BID for 7 days during the open label phase).  Our working hypothesis is that a higher dose of dexamethasone will improve dyspnea, 
respiratory function and quality of life for cancer patients compared the lower dose.
2.0 Background and Significance
B. Background and Significance
B.1. Significance of Dyspnea. Dyspnea is a subjective awareness of difficulty breathing, which may be associated with the distressing 
sensation of suffocation. It is one of the most common and most feared symptoms among cancer patients, occurring in approximately 20-
40% of patients at the time of diagnosis of advanced disease (Ripamonti et al. 1998, Tishelman et al. 2007) and in up to 70% of patients in 
the last 6 weeks of life (Ben-Aharon et al. 2008). Dyspnea is associated with fatigue, anxiety, decreased function and lower quality of life. 
Furthermore, dyspnea has been shown to be an important prognostic factor in patients with advanced cancer (Hauser et al. 2006, 
Maltoni et al. 2005). 
B.2. The Pathophysiology of Dyspnea is shown in Figure 1. The sensory cortex receives afferent input from mechanoreceptors in airways 
and the chest wall, stretch and irritant receptors in the lungs, chemoreceptors in the brainstem, and other signals from the motor cortex, 
generating the sensation of breathlessness (Mahler 2011, Manning and Schwartzstein 1995). Causes of dyspnea can be classified as 
cancer-related, treatment-related and/or psychological factors. Progressive disease may result in parenchymal metastasis, lymphangitic 
carcinomatosis, airway obstruction, atelectasis, and/or pleural effusion, all of which may cause difficulty breathing. 
B.3. The Current Management of Dyspnea involves treatment of any reversible causes and supportive measures to minimize the 
sensation of dyspnea. Relief of dyspnea can be achieved through a number of pharmacologic and non-pharmacologic measures. Common 
medications for dyspnea include opioids, bronchodilators, corticosteroids and benzodiazepines (Ben-Aharon et al. 2008, Cranston et al. 
2008, Jennings et al. 2002).  A systemic review suggested that oral and parenteral, but not nebulized, opioids are effective in managing 
dyspnea (Jennings et al. 2002). However, the potential benefit of opioids is limited by their adverse effects, including sedation and opioid-
induced neurotoxicity at higher doses. Supplemental oxygen has been shown to be efficacious only in patients with hypoxemia 
(Abernethy et al. 2010, Cranston et al. 2008).  For patients with chronic obstructive pulmonary diseases, systemic corticosteroids have been 
clearly shown to reduce respiratory symptoms, improve FEV1 and shorten hospitalization in acute exacerbations (Falk et al. 2008, 
Walters et al. 2009, Wood-Baker et al. 2007). Furthermore, inhaled steroids have been demonstrated to improve various clinical outcomes 
in COPD patients including the number of physician visits and airway hyperreactivity (Calverley et al. 2007, Lung Health Study Research 
2000, Yang et al. 2007). However, the efficacy of corticosteroids for dyspnea has not been clearly elucidated in cancer patients.
B.4. Corticosteroids for Dyspnea in Cancer Patients. No study to date has specifically examined the relationship between inflammation 
and dyspnea in cancer patients. However, cancer is known to induce host inflammatory response and often produces a number of 
cytokines with both systemic and peripheral effects (Wang et al. 2010).  Thus, cancer is similar to COPD which is also a disease 
characterized by a significantly inflammatory component, including airway wall infiltration of T lymphocytes and macrophages, increased 
lung TNFa and IL8, increased lung IL6 during exacerbations, and elevated serum leptin, IL6, TNFa, CRP, fibrinogen, peripheral neutrophil 
activation, and activation of apoptosis of peripheral lymphocytes (Falk et al. 2008).  The severity of dyspnea of COPD as determined by the 
FEV1 correlated with concentrations of IL-1b, MIP-1b, CD83, IL-1 receptor 2, and IL-1 receptor antagonist as measured by gene microarray 
(Oudijk et al. 2005).  Steroids have been shown to modulate the inflammatory response and improve dyspnea (Calverley et al. 2003, 
Lapperre et al. 2009).  More recently, a randomized controlled trial on an IL8 monoclonal antibody also found significant improvement in the 
sensation of dyspnea (Mahler et al. 2004).  The available evidence suggests that modulation of the inflammatory response may improve the 
sensation of dyspnea.  Given that inflammation is a significant mediator of dyspnea in cancer patients, we hypothesize that corticosteroids 
could have a therapeutic benefit for cancer patients. 
Few clinical studies have addressed the role of corticosteroids for dyspnea in cancer patients.  In a case series, Elsayem et al. reported 
significant improvement in dyspnea after administration of high dose steroids among patients with upper airway obstruction (Elsayem and 
Bruera 2007).  In a prospective series, Hardy et al. found that 5/13 advanced cancer patients experienced some improvement with 
dexamethasone, 6/13 had no change and 2/13 did worse (Hardy et al. 2001).  Matso et al. surveyed 120 Japanese palliative care 
physicians about their use of steroids.  37% of physicians perceived the positive effect of steroids on dyspnea to take place within 24 hours, 
38% within 1-2 days, and 24% within 3-7 days (Matsuo et al. 2011). The main perceived predictors of steroid efficacy were lymphangitic 
carcinomatosis, airway obstruction, multiple lung metastases.  The main side effects after 1 week of use were hyperglycemia, insomnia, 
delirium and oral candidiasis.  A recent systematic review on dyspnea interventions found no study on corticosteroids, and concluded that 
high quality randomized controlled trials are needed to examine the effectiveness of corticosteroids for dyspnea (Viola et al. 2008). A study 
examined the effect of prednisone in healthy men on induced dyspnea using inspiratory resistors and breathholding, and concluded that 
prednisone intake was associated with significant increase in minute ventilation during breathing compared to placebo (Kallas De 
Carvalho et al. 2002).
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B.5. Preliminary data. One of our co-investigators, Dr. Yennu, recently completed a randomized controlled trial comparing dexamethasone 
4mg twice a day versus placebo for cancer related fatigue, with dyspnea as a secondary endpoint.  Use of dexamethasone was associated 
with significant improvement in dyspnea compared to placebo.
3.0 Experimental Approach
C.1. Overall Study design. This is a 2-arm, double blind, parallel randomized controlled trial of dexamethasone and placebo for cancer 
patients with dyspnea (Figure 1).  The main goal of this study is to determine the effect size for both dexamethasone and placebo arm to 
inform a larger, adequately powered confirmatory randomized controlled trial.  For this preliminary study, we plan to enroll 20 patients per 
arm, with a total of 40 patients for the entire study (see statistical considerations for more details).  Patients will randomized to either 
dexamethasone or placebo for 7 days in a blinded fashion; this will be followed by an open label phase in which patients in both arms would 
take dexamethasone for 7 days.  The rationale for the open label phase is to give all patients an opportunity to try the study medication, and 
to examine the use of dexamethasone at a different dose as an exploratory endpoint (objective #5). Based on our experience conducting 
symptom control trials, we believe this study design is feasible and would not add undue burden for patients. To reimburse patients for 
their time and effort, we will provide a gift card for $20 per visit (day 7+/-2 and day 14+/-2).  
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C.2. Eligibility Criteria. The eligibility criteria are shown in Table 2.
Table 2. Study Eligibility Criteria
Inclusion Criteria
Diagnosis of cancer
Dyspnea with an average intensity level >3/10 on the numeric rating scale over the past week
Clinical or radiologic history of lung/pleural involvement (primary or metastatic), lymphangitic carcinomatosis or 
airway involvement secondary to tumor infiltration
Outpatients at MD Anderson Cancer Center seen by the Supportive Care, Rehabilitation Service, Thoracic Oncology 
or Pulmonary Medicine
Able to communicate in English 
Karnofsky performance status >=40%
Age 18 or older
Permission from the attending medical oncologist if the patient is currently on an interventional cancer therapy trial.
Exclusion Criteria
Delirium (i.e. Memorial delirium rating scale >13)
Oxygen saturation <90% despite supplemental oxygen >6L/min
Previous allergic reactions to dexamethasone
Uncontrolled hyperglycemia as defined by any blood glucose of >300 mg/dl in the past two weeks
Severe anemia (Hb <7g/L) not corrected prior to study enrollment (bloodwork is not required if patient did not have 
recent chemotherapy within last 2 weeks)
Post-surgical open wound that has not been healed at  the time of enrollment
Any infection requiring antibiotics within the past 2 weeks
Major surgery within the past 2 weeks
Megestrol use at the time of study enrollment
Neutropenia (absolute neutrophil count < 1.0) (bloodwork is not required if patient did not have recent chemotherapy 
within last 2 weeks)
Currently on or expected to start cytotoxic chemotherapy within 1 week of study enrollment
Chronic obstructive pulmonary disease (COPD) exacerbation at the time of study enrollment
Heart failure exacerbation at the time of study enrollment
Chronic systemic corticosteroid use (>14 days) at the time of study enrollment
Unwilling to provide informed consent
C.3. Study screening. A 2 step consent process will be used.   A verbal script is provided in the Appendix P.  First, a verbal consent will be 
obtained by the study staff to proceed with screening of potential participants for eligibility and to characterize their dyspnea using the 
dyspnea survey and the cancer dyspnea scale. Eligible patients will then be formally enrolled onto the study after they have signed the 
informed consent indicating a willingness to participate in the trial.  The number of patients screened, approached, eligible and enrolled will 
be documented.  Reasons for refusal for eligible patients will also be captured.
C.4. Randomization. A computer generated sequence in permuted blocks will be used to assign patients to either dexamethasone or 
placebo via CORe, a secured website.  We will stratify by FEV1/FVC ratio (<0.8 vs. >/= 0.8). CORe will set up a Randomization website and 
Investigational Pharmacy personnel will perform the randomization assignment. Susan Frisbee-Hume, our research manager, will provide 
the necessary CORe training for the research team. 
C.5. Blinding. Both patients and the research staff conducting the assessment will be blinded to the treatment assignment.  Placebo 
capsules identical to dexamethasone 4mg capsules in appearance and taste will be compounded by Green Park Compounding Pharmacy, 
and both will be dispensed by Investigational Pharmacy at MD Anderson.  At the end of the blinded phase, we will assess blinding by 
asking patients which study arm they believe they have been randomized to.
C.6. Research staff. An orientation will be held with research staff involved in this study to introduce them with the study design, and 
standardize the provision of each intervention.  
C.7. Study Interventions. The intervention arm will receive dexamethasone 8 mg (2 capsules of 4 mg) given orally twice a day for 4 days, 
then 4 mg given orally twice a day for 3 days.  This dose was chosen partly based on our feasibility data demonstrating that 
dexamethasone improved dyspnea.  
Dexamethasone is a commonly used medication in cancer patients.  It is approved by the US Food and Drug Administration for 
treatment of multiple indications, including allergic disorder (including asthma), cerebral edema associated with primary or metastatic brain 
tumor, craniotomy, or head injury, collagen disease, disorder of ear, disorder of endocrine system, disorder of eye, disorder of 
gastrointestinal tract, disorder of hematopoietic structure, disorder of respiratory system (treatment of berylliosis, fulminating or 
disseminated pulmonary tuberculosis (when used concurrently with appropriate antituberbulosis therapy), idiopathic eosinophilic 
pneumonias and symptomatic sarcoidosis, Loeffler's syndrome not manageable by other means and aspiration pneumonitis), disorder of 
skin, exacerbation of multiple sclerosis, hypercalcemia of malignancy, idiopathic thrombocytopenic purpura, inflammatory disorder of 
musculoskeletal system, macular retinal edema, mycosis fungoides, neoplastic disease, palliative management of leukemias and 
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lymphomas, nephrotic syndrome, Idiopathic or due to lupus erythematosus without uremia, non-infectious posterior uveitis, trichinosis with 
neurologic or myocardial involvement, tuberculosis of meninges with subarachnoid block or impending block when used concurrently with 
antituberculosis therapy 
(http://www.thomsonhc.com/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/7CB60A/ND_AppProduct/evidencexpert
/DUPLICATIONSHIELDSYNC/0CC381/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/evidencexpert.Display
DrugdexDocument?docId=0221&contentSetId=31&title=Dexamethasone&servicesTitle=Dexamethasone&topicId=clinicalApplicationsSectio
n&subtopicId=therapeuticUsesSection#4.5.A.74).  However, it has not been specifically approved for management of dyspnea.
Dexamethasone is commonly used in oncology practice for management of cerebral edema, spinal cord compression, chemotherapy 
induced nausea and vomiting, bowel obstruction, pain, anorexia, dyspnea and fatigue. For patients with chronic obstructive pulmonary 
diseases, systemic corticosteroids have been clearly shown to reduce respiratory symptoms, improve FEV1 and shorten hospitalization in 
acute exacerbations (Falk et al. 2008, Walters et al. 2009, Wood-Baker et al. 2007). Furthermore, inhaled steroids have been demonstrated 
to improve various clinical outcomes in COPD patients including the number of physician visits and airway hyperreactivity (Calverley et al. 
2007, Lung Health Study Research 2000, Yang et al. 2007). However, the efficacy of corticosteroids for dyspnea has not been clearly 
elucidated in cancer patients.
Our study proposes to use oral dexamethasone for the management of dyspnea.  The dose of dexamethasone we plan to use is 8mg 
PO BID for 4 days, then 4 mg PO BID x10 more days.  This is similar to doses we use for CINV prophylaxis (8-20mg IV/PO prior to 
chemotherapy, then 4-8mg q12h for up to 4 days after chemotherapy) (Mullin and Beckwith, 
www.ifvrh.com/policies_quick_ref/Treatment_of_CINV.html). This is study is purely exploratory in nature, and we do not plan to seek FDA 
approval for the new indication of dyspnea.
The control arm will receive placebo capsules prepared by a compounding pharmacy (Green Park Compounding Pharmacy) identical in 
appearance to dexamethasone 4 mg capsules, and will be instructed to take two capsules twice a day for 4 days, followed by one capsule 
twice a day for 3 days.  
In the open label phase, patients assigned to either arm will be asked to take dexamethasone 4 mg orally twice a day for 7 days.  Both 
dexamethasone and placebo capsules used throughout this study will be compounded by Green Park Compounding Pharmacy and 
dispensed by Investigational Pharmacy at MD Anderson. Dexamethasone/placebo capsules will be provided free of charge to patients 
during the 14 day study period. 
C.8. Medication use during study.  We will ask patients to record the use of study medications using a medication diary.  We will also 
keep track of their adherence by asking them to bring their medication boxes for a pill count. Phone call reminders will be provided 
daily.  To document the co-intervention effect on dyspnea, patient use of regular and breakthrough opioids (for any reason) and 
bronchodilators at enrollment and during the study. Patients will receive daily phone calls for reminders and assessments.  They can take it 
as soon as possible if they forget a dose.
C.9. Feasibility endpoints. Our primary objective is to test the feasibility of a protocol that uses dexamethasone and placebo for dyspnea, 
and to determine the feasibility of these two interventions for advanced cancer patients with persistent dyspnea.  We will document the 
following:
·
Rates of recruitment and retention (see section D1).
·
Reasons for refusal and dropout
·
Outcome measure—we will compare the sensitivity of Numeric rating scale and Borg scale to change, and identify key measure for 
future study
·
Participant satisfaction—participants will provide an opinion regarding their satisfaction with study overall
C.10. Study assessments. See Table 4 for a detailed description of all study assessments. 
Table 4. Summary of Study Assessments
Assessments
Baseline   (In 
person)
Day 4+/-2      (by 
phone)
Day 7+/-2      (In 
person/by phone)
Day 14+/-2     (In 
person/by phone)
Demographics 
and 
Cancer Diagnosis1
X
Medication History2
X
Karnofsky 
Performance Status3
X
Dyspnea Survey4
X
O2 saturation and 
Respiratory Rate
X
Cancer 
Dyspnea 
Scale5
X
X
X
X
Edmonton Symptom 
Assessment Scale6
X
X
X
X
Dyspnea 
Numeric 
Rating Scale7
Daily 
Assessment
Dyspnea Borg scale8
X
X
X
X
Spirometry 
Measures9
X
X
X
X
EORTC QLQ-C3010
X
X
X
X
Adverse effects11
X
X
X
Global assessment12
X
X
X
Pill count
X
X
Check of blinding
X
1 patient initials, medical record number, date of birth, sex, race, education, marital status, cancer diagnosis, co-morbidities, cause(s) of dyspnea.
2 medications that could be used to treat dyspnea, including scheduled and as needed opioids, bronchodilators, and steroids will be documented.
3 an 11-point assessment scale that rates patients’ functional status between 0% (death) and 100% (completely asymptomatic) based on their ambulation, activity level, 
and disease severity (Schag et al. 1984).
4 characterization of patients dyspnea including the following: presence of dyspnea at rest, average dyspnea in last 24 hours, worse dyspnea in last 24 hours, best 
dyspnea in last 24 hours, number of episodes of exacerbation per day, triggers of breakthrough dyspnea, average duration of each episode, current treatment for 
breakthrough dyspnea.  It also adopted 3 questions from EORTC Lung module about dyspnea.
5 validated 12-item questionnaire specifically designed to assess the quality of dyspnea in cancer patients during the past few days (Tanaka et al. 2000). Each item has a 
score between 1 and 5, for a maximum of 60. There are sub-scores for sense of effort, anxiety, and discomfort. 
6 validated questionnaire that measures 10 common symptoms in the past 4 hours (pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, 
sleep, and feeling of well being) using numeric rating scales (Bruera et al. 1991).
7 a 0 (no dyspnea) to 10 (worst dyspnea) categorical scale validated for rating the severity of dyspnea (Dorman et al. 2007, Gift and Narsavage 1998, Powers and Bennett 
1999).  
8 a 0 to 10 categorical scale for rating the severity of dyspnea. It is a ratio scale with descriptive anchors throughout the range in which a rating of 8 signifies 
breathlessness twice as severe as 4, which in turn is twice as severe as 2 (Dorman et al. 2007, Gift and Narsavage 1998, Kendrick et al. 2000, Powers and Bennett 
1999).  
9 the MicroLoop Spirometer (Micro Direct Inc, Lewiston, ME) will be used at baseline, day 7 and day 14.  It is approved by the American Thoracic Society and US Food 
and Drug Administration.  Various spirometry parameters will be obtained, such as vital capacity (VC), forced expiratory volume in 1 second (FEV1), forced vital capacity 
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(FVC), FEV1/FVC, peak inspiratory flow, and peak expiratory flow.  As an exploratory measure, patients will also be asked to use the portable Microlife PF 100 Peak Flow 
Meter (Microlife, Clearwater, FL) to measure peak flow and FEV1 on a daily basis. 
10 a well-validated quality of life instrument for cancer patients, consisting of 30 items that encompasses 3 symptom scales (pain, fatigue, nausea/vomiting), 6 single-item 
symptom items, 5 functional scales (physical, cognitive, role, emotional, and social), and one scale assessing global health status/quality of life. Each scale consists of 2-5 
items.  All items have four response categories (not at all, a little, quite a bit, very much), except for 2 items assessing overall health status/quality of life, which use a 
seven-point scale.
11 adverse effects related to the use of dexamethasone, such as edema, fever, infections, insomnia, anxiety, personality change, dyspepsia will be rated using the 
National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
12 patients will be asked about their dyspnea (worse, about the same, or better) comparing the level of dyspnea before and after the study (Guyatt et al. 1993, 
Redelmeier et al. 1996).
13 patients will be asked be record their study medication use, as well as any use of opioids and bronchodilators for relief of dyspnea.
C.11. Patient Safety, Monitoring, and Confidentiality. Prior to study initiation, all research staff participating in this study will receive an 
orientation to the devices and forms in this study to ensure consistent assessments.  During the study, trained research staff will be 
performing study assessments and monitoring the patient carefully throughout the study period. In addition to daily phone calls, patients will 
be given the contact information of the research nurse in case they develop any significant adverse effects, and will be treated as they arise 
as per clinical practice.  The study may be discontinued at the discretion of the treating physician or study principal investigator.  Regulatory 
monitoring will be provided by the principal investigator, the Institutional Review Board, and the Data Safety and Monitoring Board. Patient 
confidentiality will be ensured by use of patient initials, secure storage of clinical data, and anonymous reporting.
4.0 Statistical Analysis
D.1. Sample Size Calculation. This pilot study is based on a convenience sample of 20 subjects per arm.  
D.2. Data Analysis
Primary Objective: Our primary objective is to determine the completion rate for patients enrolling in this study.  Patients who complete the 
dyspnea NRS on day 72 will be counted as successes.  Dropouts are defined as subjects who do not complete the dyspnea NRS on day 7 
+/- 2, and will be counted as failures toward the feasibility outcome.  We will declare the study as feasible if we observe at least 20 
successes, based on a recent review of Supportive Oncology studies in our department in which we found that approximately 50% patients 
completed their interventional clinical trial.
Objective #2. We will test our hypothesis that 4 days of dexamethasone will improve dyspnea, respiratory function and quality of life for 
cancer patients using paired t-tests.
Objective #3. We will test our hypothesis that 7 days of dexamethasone will improve dyspnea, respiratory function and quality of life for 
cancer patients using paired t-tests. A sample size of 20 per arm will allow us to detect an effect size of 0.9 in the change of dyspnea NRS 
between baseline and day 7 with an 80% power and an alpha of 5%, assuming a standard deviation of 2.  
Objective #4. We will test our hypothesis that dexamethasone will improve dyspnea, respiratory function and quality of life for cancer 
patients compared to placebo using two-sample t-tests on the differences between baseline and 4 and 7 days for each outcome measure.
Objective #5.  We will test our hypothesis that increased dose results in better outcomes by comparing the first 7 days of treatment arm to 
the last seven days of the placebo arm.  We will  use two-sample t-tests on the differences between baseline (day 0 for treatment arm, day 
7 for placebo arm) and 7 days later (day 7 for treatment arm, day 14 for placebo arm).
5.0 Data Confidentiality Procedures
Health information will be protected and we will maintain the confidentiality of the data obtained from the patient's chart.  
Collection of identifiers: We will collect and securely store patients' identifiers (including name, medical record number and demographic 
specifications).  Each patient will be assigned a study number that will be the only identifier to figure in the analytical file and personal data 
will not be disclosed in any form. The key linking these numbers will be retained in a securely locked file by the investigator.
Data Storage: Protection of electronic and paper records will be guaranteed. All electronic records will be stored on password-protected 
institution computers behind the institution firewall.  Any paper records will be classified and stored in locked files inside a locked office.
Training of personnel: Only MDACC personnel trained in maintaining confidentiality, the principle investigators and co-investigators, will 
have access to study records.
Data sharing: Study data will not be shared with any individuals or entities. The data will be kept by the principle investigator in a locked 
file cabinet.
Final disposition of study records: These data will be used only for this research study data files will be destroyed 5 years after 
publication of the findings.
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