Buspirone in Reducing Shortness of Breath in Patients With Cancer

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT00053846
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 432
• Locations: 15
• Arms: 2
• Duration (Months): 98
• Patients Per Site: 28.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Buspirone may be effective in reducing dyspnea (shortness of breath) in patients with cancer who are undergoing chemotherapy.

PURPOSE: Randomized clinical trial to study the effectiveness of buspirone in reducing shortness of breath in patients who are undergoing chemotherapy for cancer.

Condition or Disease	Intervention/Treatment	Phase
Dyspnea; Pulmonary Complications; Unspecified Adult Solid Tumor, Protocol Specific	Drug: buspirone hydrochloride; Drug: Placebo	Phase 2/Phase 3

Detailed Description

OBJECTIVES:

• Assess the degree to which buspirone can decrease the sensation of dyspnea in patients with malignant disease.

• Estimate the incidence of dyspnea in patients seen in community oncology practice settings.

• Investigate interrelationships of fatigue, depression, anxiety, and patient report of dyspnea.

• Assess the quality of life of patients treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center (CCOP site). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Beginning on day 7 of chemotherapy, patients receive oral buspirone once a day for 3 days and then twice daily for up to 28 days.

• Arm II: Patients receive oral placebo as in arm I. Dyspnea is assessed at baseline. Dyspnea, mood, fatigue, depression, anxiety, and quality of life are assessed within 5-7 days before chemotherapy and immediately following therapy.

PROJECTED ACCRUAL: A total of 376 patients (188 per treatment arm) will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 432 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Supportive Care
• Official Title: Buspirone in Reducing Shortness of Breath in Patients With Cancer
• Study Start Date: Nov 1, 2002
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: buspirone hydrochloride buspirone hydrochloride	Drug: buspirone hydrochloride; The dose of buspirone will be 10 mg taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the 28 day study period
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Dyspnea as Measured by Oxygen Cost Diagram (OCD) [28 days after beginning study drug or placebo]

   OCD was used to evaluate dyspnea on exertion and activities of daily living. OCD is a visual analog scale for quantifying a patient's evaluation of tolerance of exertion, which corresponds to oxygen requirements at different activity levels. It is measured as a score of 2 (sleeping) to 14 (brisk walking uphill). HIgher scores indicate fewer limitations due to dyspnea.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of cancer

• Treatment includes the following scenarios:

• May have had prior chemotherapy course(s)

• Scheduled to receive at least 2 courses of chemotherapy

• Courses may include multiple treatment days such as days 1-5 or day 1-day 8 regimens and may include oral regimens

• Dyspnea as a symptom within the past 5 days (defined by a score of at least grade 2 on the Modified Medical Research Council Dyspnea Scale)

• All underlying causes of dyspnea have received medical treatment per best clinical judgement of treating physician

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Eastern Cooperative Oncology Group 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Adequate hepatic function (determined by treating oncologist)

Renal

• Adequate renal function (determined by treating oncologist)

Cardiovascular

• Adequate cardiac function (determined by treating oncologist)

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No history of mania or seizures

• No prior hospitalization for any psychiatric condition

• No prior hypersensitivity to buspirone

• Able to swallow medication

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Concurrent radiotherapy allowed

Surgery

• Not specified

Other

• At least 2 weeks since prior and no concurrent monoamine oxidase inhibitors (MAOIs)

• Concurrent narcotic medications allowed

• Concurrent benzodiazepine medications allowed

• Concurrent serotonin reuptake inhibitors allowed

• No concurrent alcohol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MBCCOP - University of Illinois at Chicago	Chicago	Illinois	United States	60612-7323
2	CCOP - Central Illinois	Decatur	Illinois	United States	62526
3	CCOP - Evanston	Evanston	Illinois	United States	60201
4	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
5	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
6	CCOP - Kansas City	Kansas City	Missouri	United States	64131
7	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
8	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
9	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
10	CCOP - Dayton	Dayton	Ohio	United States	45429
11	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
12	CCOP - Greenville	Greenville	South Carolina	United States	29615
13	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
14	CCOP - Northwest	Tacoma	Washington	United States	98405-0986
15	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• University of Rochester
• National Cancer Institute (NCI)

Investigators

• Study Chair: Peter Bushunow, MD, University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary Morrow, Director, URCC CCOP Research Base, University of Rochester
• ClinicalTrials.gov Identifier: NCT00053846
• Other Study ID Numbers: CDR0000269487; U10CA037420; URCC U1701
• First Posted: Feb 6, 2003
• Last Update Posted: Nov 24, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Gary Morrow, Director, URCC CCOP Research Base, University of Rochester: dyspnea; pulmonary complications; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Dyspnea; Buspirone

Study Results

Participant Flow

Arm/Group Title	Buspirone Hydrochloride	Placebo
Arm/Group Description	buspirone hydrochloride: The dose of buspirone will be 10 mg taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the 28 day study period	Treatment with placebo will be one tablet taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the study period.
Period Title: Overall Study
STARTED	213	219
COMPLETED	187	192
NOT COMPLETED	26	27

Baseline Characteristics

Arm/Group Title	Buspirone Hydrochloride	Placebo	Total
Arm/Group Description	buspirone hydrochloride: The dose of buspirone will be 10 mg taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the 28 day study period	Treatment with placebo will be one tablet taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the study period.	Total of all reporting groups
Overall Participants	187	192	379
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.9 (10.3)	64.0 (9.4)	63.5 (9.9)
Sex: Female, Male (Count of Participants)
Female	100 53.5%	95 49.5%	195 51.5%
Male	87 46.5%	97 50.5%	184 48.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 1%	2 0.5%
Not Hispanic or Latino	181 96.8%	189 98.4%	370 97.6%
Unknown or Not Reported	6 3.2%	1 0.5%	7 1.8%
Race/Ethnicity, Customized (participants) [Number]
White	166 88.8%	171 89.1%	337 88.9%
African American	19 10.2%	20 10.4%	39 10.3%
Other	2 1.1%	1 0.5%	3 0.8%
Marital Status (participants) [Number]
Married	127 67.9%	126 65.6%	253 66.8%
Not Married	60 32.1%	66 34.4%	126 33.2%
Education (participants) [Number]
Beyond High School	76 40.6%	78 40.6%	154 40.6%
High School or Less	111 59.4%	114 59.4%	225 59.4%
History of chronic obstructive pulmonary disease (COPD) (participants) [Number]
Yes	28 15%	69 35.9%	97 25.6%
No	159 85%	123 64.1%	282 74.4%
Tumor Site (participants) [Number]
Lung	114 61%	118 61.5%	232 61.2%
Breast	25 13.4%	27 14.1%	52 13.7%
Gastrointestinal	18 9.6%	17 8.9%	35 9.2%
Other	30 16%	30 15.6%	60 15.8%
Tumor Stage (participants) [Number]
I	10 5.3%	12 6.3%	22 5.8%
II	17 9.1%	18 9.4%	35 9.2%
III	49 26.2%	53 27.6%	102 26.9%
IV	103 55.1%	102 53.1%	205 54.1%
Unknown	8 4.3%	7 3.6%	15 4%
O2 Cost Diagram (OCD) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.70 (2.6)	8.43 (2.6)	8.56 (2.6)
Modified Medical Research Council Dyspnea Scale (MMRCDS) Grade (participants) [Number]
0	4 2.1%	2 1%	6 1.6%
1	21 11.2%	23 12%	44 11.6%
2	77 41.2%	80 41.7%	157 41.4%
3	61 32.6%	54 28.1%	115 30.3%
4	22 11.8%	32 16.7%	54 14.2%
Unknown	2 1.1%	1 0.5%	3 0.8%

Outcome Measures

1. Primary Outcome

Title	Dyspnea as Measured by Oxygen Cost Diagram (OCD)
Description	OCD was used to evaluate dyspnea on exertion and activities of daily living. OCD is a visual analog scale for quantifying a patient's evaluation of tolerance of exertion, which corresponds to oxygen requirements at different activity levels. It is measured as a score of 2 (sleeping) to 14 (brisk walking uphill). HIgher scores indicate fewer limitations due to dyspnea.
Time Frame	28 days after beginning study drug or placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone Hydrochloride	Placebo
Arm/Group Description	buspirone hydrochloride: The dose of buspirone will be 10 mg taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the 28 day study period	Treatment with placebo will be one tablet taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the study period.
Measure Participants	187	192
Mean (Standard Deviation) [units on a scale]	8.98 (2.85)	9.32 (2.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buspirone Hydrochloride, Placebo
	Comments	H0: The true difference in means is equal to zero. Ha: The true difference in means is not equal to zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.483
	Confidence Interval	(2-Sided) 95%; -1.020 to 0.0576
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2750
	Estimation Comments	Multiple Imputation (MI) used for estimates. MICE software in R was used to generate 100 imputed datasets. ANCOVA was run on each, and results were pooled.

Adverse Events

Arm/Group Title	Buspirone Hydrochloride		Placebo
Arm/Group Description	buspirone hydrochloride: The dose of buspirone will be 10 mg taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the 28 day study period		Treatment with placebo will be one tablet taken by mouth at bedtime for 3 days, then twice each day, in the morning and at bedtime for the remainder of the study period.
All Cause Mortality
	Buspirone Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Buspirone Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/213 (1.4%)		3/219 (1.4%)
Gastrointestinal disorders
Esophagitis	0/213 (0%)		1/219 (0.5%)
General disorders
Anemia & pleural effusion, inc SOB	1/213 (0.5%)		0/219 (0%)
Scrotal pain/swelling; hypoxia; death	0/213 (0%)		1/219 (0.5%)
Death	2/213 (0.9%)		3/219 (1.4%)
Respiratory, thoracic and mediastinal disorders
Breathlessness & Chest Pressure	1/213 (0.5%)		0/219 (0%)
Pulmonary embolism	1/213 (0.5%)		1/219 (0.5%)
Other (Not Including Serious) Adverse Events
	Buspirone Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/213 (6.1%)		10/219 (4.6%)
Blood and lymphatic system disorders
Neutropenia	1/213 (0.5%)		0/219 (0%)
Low platelet count	1/213 (0.5%)		0/219 (0%)
Hypoxemia	1/213 (0.5%)		0/219 (0%)
Orthostatis hypotension	0/213 (0%)		1/219 (0.5%)
Thrombosis	1/213 (0.5%)		0/219 (0%)
Gastrointestinal disorders
GI Bleed	0/213 (0%)		1/219 (0.5%)
Nausea and vomitting	3/213 (1.4%)		1/219 (0.5%)
Esophagitis	0/213 (0%)		3/219 (1.4%)
General disorders
Aching hands and back	0/213 (0%)		1/219 (0.5%)
Disease progression	0/213 (0%)		1/219 (0.5%)
Shakes and tremors	0/213 (0%)		2/219 (0.9%)
Infections and infestations
Pneumonia/bronchitis	1/213 (0.5%)		0/219 (0%)
Nervous system disorders
Dizziness, confusion; insomnia	2/213 (0.9%)		2/219 (0.9%)
Confusion	1/213 (0.5%)		0/219 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/213 (1.4%)		2/219 (0.9%)
Skin and subcutaneous tissue disorders
Cellulitis	1/213 (0.5%)		0/219 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.