S1202: Duloxetine Hydrochloride for Muscle/Joint Pain in Early-Stage Breast Cancer Receiving Hormone Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01598298

Recruitment Status : Completed

First Posted : May 15, 2012

Results First Posted : February 28, 2018

Last Update Posted : December 16, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Southwest Oncology Group

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Conditions	Breast Cancer Musculoskeletal Complications Pain
Interventions	Drug: duloxetine hydrochloride Other: placebo
Enrollment	299

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm I: Duloxetine	Arm II: Placebo
Arm/Group Description	Patients receive duloxetine hydroch...	Patients receive placebo PO QD on d...
Arm/Group Description	Patients receive duloxetine hydrochloride orally (PO) once daily (QD) on days 1-7, twice daily (BID) on days 8-84, and then QD on days 85-91. duloxetine hydrochloride: Given PO	Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91. placebo: Given PO
Period Title: Overall Study
Started	150	149
Patients Evaluable for Primary Endpoint ^[1]	127	128
Patients Evaluable for Adverse Events	138	141
Completed	110	108
Not Completed	40	41
Reason Not Completed
Not eligible	5	5
Adverse Event	21	19
Progression/relapse	0	2
Withdrawal by Subject	10	15
Other reason (not protocol specified)	4	0
[1] Patient has an in-window BPI assessment at week 2, 6, or 12.

Baseline Characteristics

Arm/Group Title		Arm I: Duloxetine	Arm II: Placebo	Total
Arm/Group Description		Patients receive duloxetine hydroch...	Patients receive placebo PO QD on d...	Total of all reporting groups
Arm/Group Description		Patients receive duloxetine hydrochloride orally (PO) once daily (QD) on days 1-7, twice daily (BID) on days 8-84, and then QD on days 85-91. duloxetine hydrochloride: Given PO	Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91. placebo: Given PO	Total of all reporting groups
Overall Number of Baseline Participants		145	144	289
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Eligible patients
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	145 participants	144 participants	289 participants
		60 (40 to 83)	60 (27 to 82)	60 (27 to 83)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	145 participants	144 participants	289 participants
	Female	145 100.0%	144 100.0%	289 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	145 participants	144 participants	289 participants
	Hispanic or Latino	5 3.4%	6 4.2%	11 3.8%
	Not Hispanic or Latino	140 96.6%	137 95.1%	277 95.8%
	Unknown or Not Reported	0 0.0%	1 0.7%	1 0.3%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	145 participants	144 participants	289 participants
	American Indian or Alaska Native	0 0.0%	2 1.4%	2 0.7%
	Asian	6 4.1%	3 2.1%	9 3.1%
	Native Hawaiian or Other Pacific Islander	1 0.7%	0 0.0%	1 0.3%
	Black or African American	10 6.9%	17 11.8%	27 9.3%
	White	128 88.3%	120 83.3%	248 85.8%
	More than one race	0 0.0%	1 0.7%	1 0.3%
	Unknown or Not Reported	0 0.0%	1 0.7%	1 0.3%
Baseline pain score ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	145 participants	144 participants	289 participants
	4-6	110 75.9%	110 76.4%	220 76.1%
	7-10	35 24.1%	34 23.6%	69 23.9%
		[1] Measure Description: Baseline pain score is the patient's self-reported average pain at baseline as measured by the BPI-SF question, "Please rate your joint pain by selecting the one number that best describes your joint pain on the AVERAGE". This score ranges from 0 to 10, with higher scores indicating more pain.
Prior taxane use Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	145 participants	144 participants	289 participants
	No	68 46.9%	65 45.1%	133 46.0%
	Yes	77 53.1%	79 54.9%	156 54.0%

Outcome Measures

1.Primary Outcome


Title	Average Joint Pain According to BPI-SF
Description	Average joint pain according to the Brief Pain Inventory - Short Form ...
Description	Average joint pain according to the Brief Pain Inventory - Short Form (BPI-SF) average pain score (item #4). This item has a scale of 0 to 10 with 0 indicating "No pain" and 10 indicating "Pain as bad as you can imagine".
Time Frame	Weeks 2, 6, 12, and 24; Week 12 reported

Outcome Measure Data

Analysis Population Description

Patients evaluable for primary endpoint


Arm/Group Title	Arm I: Duloxetine	Arm II: Placebo
Arm/Group Description:	Patients receive duloxetine hydroch...	Patients receive placebo PO QD on d...
Arm/Group Description:	Patients receive duloxetine hydrochloride orally (PO) once daily (QD) on days 1-7, twice daily (BID) on days 8-84, and then QD on days 85-91. duloxetine hydrochloride: Given PO	Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91. placebo: Given PO
Overall Number of Participants Analyzed	127	128
Mean (Standard Deviation) Unit of Measure: units on a scale
	2.9 (2.1)	3.5 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Duloxetine, Arm II: Placebo
	Comments	The primary analysis will rely on longitudinal measures of BPI at Weeks 2, 6, and 12 for improved power. Assessment windows of +/- 7 days, +/- 14 days, and +/- 14 days will be allowed for the 2, 6, and 12 week timepoints. The analysis will be performed using mixed models, adjusted for the stratification factors.
	Type of Statistical Test	Other
	Comments	Two-sided test at the alpha=0.05 level

Statistical Test of Hypothesis	P-Value	0.0002
	Comments	Two-sided p-value; alpha=0.05
	Method	Mixed Models Analysis
	Comments	Adjusted for the protocol-specified stratification factors (baseline average pain and prior taxane use)

Method of Estimation	Estimation Parameter	Coefficient for treatment term
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95% -1.24 to -0.40
	Estimation Comments	The estimation parameter is the model-based coefficient for the treatment term, with placebo as the reference level.

2.Secondary Outcome


Title	Worst Joint Pain According to the BPI-SF
Description	Worst joint pain according to the BPI-SF worst pain score (item #2). T...
Description	Worst joint pain according to the BPI-SF worst pain score (item #2). This item has a scale of 0 to 10 with 0 indicating "No pain" and 10 indicating "Pain as bad as you can imagine".
Time Frame	Weeks 2, 6, 12, and 24; Week 12 reported

Outcome Measure Data

Analysis Population Description

Patients evaluable for primary endpoint


Arm/Group Title	Arm I: Duloxetine	Arm II: Placebo
Arm/Group Description:	Patients receive duloxetine hydroch...	Patients receive placebo PO QD on d...
Arm/Group Description:	Patients receive duloxetine hydrochloride orally (PO) once daily (QD) on days 1-7, twice daily (BID) on days 8-84, and then QD on days 85-91. duloxetine hydrochloride: Given PO	Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91. placebo: Given PO
Overall Number of Participants Analyzed	127	128
Mean (Standard Deviation) Unit of Measure: units on a scale
	4.0 (2.8)	4.9 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Duloxetine, Arm II: Placebo
	Comments	The primary analysis will rely on longitudinal measures of BPI at Weeks 2, 6, and 12 for improved power. Assessment windows of +/- 7 days, +/- 14 days, and +/- 14 days will be allowed for the 2, 6, and 12 week timepoints. The analysis will be performed using mixed models, adjusted for baseline worst pain score and the stratification factors.
	Type of Statistical Test	Other
	Comments	Two-sided test at the alpha=0.05 level

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Two-sided p-value; alpha=0.05
	Method	Mixed Models Analysis
	Comments	Adjusted for baseline worst pain score and the protocol-specified stratification factors (baseline average pain and prior taxane use).

Method of Estimation	Estimation Parameter	Coefficient for treatment term
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95% -1.57 to -0.55
	Estimation Comments	The estimation parameter is the model-based coefficient for the treatment term, with placebo as the reference level.

3.Secondary Outcome


Title	Pain Interference According to the BPI-SF
Description	Pain interference according to the BPI-SF: this item has a scale of 0 ...
Description	Pain interference according to the BPI-SF: this item has a scale of 0 to 10 with 0 indicating "Does not interfere" and 10 indicating "Completely interferes".
Time Frame	Weeks 2, 6, 12, and 24; Week 12 reported

Outcome Measure Data

Analysis Population Description

Patients evaluable for primary endpoint


Arm/Group Title	Arm I: Duloxetine	Arm II: Placebo
Arm/Group Description:	Patients receive duloxetine hydroch...	Patients receive placebo PO QD on d...
Arm/Group Description:	Patients receive duloxetine hydrochloride orally (PO) once daily (QD) on days 1-7, twice daily (BID) on days 8-84, and then QD on days 85-91. duloxetine hydrochloride: Given PO	Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91. placebo: Given PO
Overall Number of Participants Analyzed	127	128
Mean (Standard Deviation) Unit of Measure: units on a scale
	1.9 (2.2)	2.6 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Duloxetine, Arm II: Placebo
	Comments	The primary analysis will rely on longitudinal measures of pain interference scores at Weeks 2, 6, and 12 for improved power. Assessment windows of +/- 7 days, +/- 14 days, and +/- 14 days will be allowed for the 2, 6, and 12 week timepoints. The analysis will be performed using mixed models, adjusted for baseline pain interference score and the stratification factors.
	Type of Statistical Test	Other
	Comments	Two-sided test at the alpha=0.05 level

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Two-sided p-value; alpha=0.05
	Method	Mixed Models Analysis
	Comments	Adjusted for baseline pain interference score and the protocol-specified stratification factors (baseline average pain and prior taxane use).

Method of Estimation	Estimation Parameter	Coefficient fro treatment term
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 95% -1.35 to -0.55
	Estimation Comments	The estimation parameter is the model-based coefficient for the treatment term, with placebo as the reference level.

Adverse Events

Time Frame	Up to 24 weeks
Adverse Event Reporting Description	Only adverse events and serious adverse events that are possibly, probably or definitely related to study drug are reported.

Arm/Group Title	Arm II: Placebo	Arm I: Duloxetine
Arm/Group Description	Patients receive placebo PO QD on d...	Patients receive duloxetine hydroch...
Arm/Group Description	Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91. placebo: Given PO	Patients receive duloxetine hydrochloride orally (PO) once daily (QD) on days 1-7, twice daily (BID) on days 8-84, and then QD on days 85-91. duloxetine hydrochloride: Given PO
All-Cause Mortality
	Arm II: Placebo	Arm I: Duloxetine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/141 (0.00%)	0/138 (0.00%)
Serious Adverse Events Serious Adverse Events
	Arm II: Placebo	Arm I: Duloxetine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/141 (0.00%)	0/138 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm II: Placebo	Arm I: Duloxetine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	83/141 (58.87%)	115/138 (83.33%)
Ear and labyrinth disorders
Vertigo ^†	6/141 (4.26%)	10/138 (7.25%)
Gastrointestinal disorders
Abdominal pain ^†	6/141 (4.26%)	11/138 (7.97%)
Constipation ^†	9/141 (6.38%)	23/138 (16.67%)
Diarrhea ^†	10/141 (7.09%)	21/138 (15.22%)
Dry mouth ^†	20/141 (14.18%)	38/138 (27.54%)
Nausea ^†	12/141 (8.51%)	47/138 (34.06%)
Vomiting ^†	2/141 (1.42%)	7/138 (5.07%)
General disorders
Fatigue ^†	25/141 (17.73%)	52/138 (37.68%)
Flu like symptoms ^†	1/141 (0.71%)	12/138 (8.70%)
Pain ^†	23/141 (16.31%)	27/138 (19.57%)
Metabolism and nutrition disorders
Anorexia ^†	3/141 (2.13%)	13/138 (9.42%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†	26/141 (18.44%)	31/138 (22.46%)
Joint range of motion decreased ^†	13/141 (9.22%)	15/138 (10.87%)
Myalgia ^†	18/141 (12.77%)	32/138 (23.19%)
Pain in extremity ^†	5/141 (3.55%)	8/138 (5.80%)
Nervous system disorders
Dizziness ^†	5/141 (3.55%)	20/138 (14.49%)
Headache ^†	30/141 (21.28%)	35/138 (25.36%)
Lethargy ^†	1/141 (0.71%)	9/138 (6.52%)
Paresthesia ^†	10/141 (7.09%)	7/138 (5.07%)
Somnolence ^†	4/141 (2.84%)	14/138 (10.14%)
Tremor ^†	0/141 (0.00%)	11/138 (7.97%)
Psychiatric disorders
Agitation ^†	7/141 (4.96%)	10/138 (7.25%)
Insomnia ^†	12/141 (8.51%)	22/138 (15.94%)
Respiratory, thoracic and mediastinal disorders
Cough ^†	6/141 (4.26%)	8/138 (5.80%)
Nasal congestion ^†	8/141 (5.67%)	7/138 (5.07%)
Skin and subcutaneous tissue disorders
Hyperhidrosis ^†	5/141 (3.55%)	13/138 (9.42%)
Vascular disorders
Hot flashes ^†	22/141 (15.60%)	33/138 (23.91%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Leukemia Committee Statistician
Organization:	SWOG Statistics and Data Management Center
Phone:	2066674623
EMail:	amoseley@fredhutch.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow DM, Sharer CW, Burton GV, Kuzma CS, Moseley A, Lew DL, Fisch MJ, Moinpour CM, Hershman DL, Wade JL 3rd. Randomized, Multicenter, Placebo-Controlled Clinical Trial of Duloxetine Versus Placebo for Aromatase Inhibitor-Associated Arthralgias in Early-Stage Breast Cancer: SWOG S1202. J Clin Oncol. 2018 Feb 1;36(4):326-332. doi: 10.1200/JCO.2017.74.6651. Epub 2017 Nov 14.

Layout table for additonal information

Responsible Party:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT01598298
Other Study ID Numbers:	S1202 S1202 ( Other Identifier: SWOG ) U10CA037429 ( U.S. NIH Grant/Contract ) NCI-2012-01960 ( Other Identifier: NCI )
First Submitted:	May 11, 2012
First Posted:	May 15, 2012
Results First Submitted:	January 31, 2018
Results First Posted:	February 28, 2018
Last Update Posted:	December 16, 2022

To Top