Conditions: Breast Cancer Musculoskeletal Complications Pain
Keywords: estrogen receptor-positive breast cancer progesterone receptor-positive breast cancer stage IA breast cancer stage IB breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer pain musculoskeletal complications
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 299
Healthy volunteers: no

Brief summary:
RATIONALE: Duloxetine hydrochloride may lessen muscle, bone, and joint pain caused by hormone therapy. It is not yet known whether duloxetine hydrochloride is more effective than a placebo in treating patients with muscle, bone, and joint pain caused by hormone therapy.

PURPOSE: This randomized phase III trial studies how well duloxetine hydrochloride works compared to a placebo in treating muscle, bone, and joint pain in patients with early-stage breast cancer receiving hormone therapy.

Detailed description:
OBJECTIVES:

Primary

* To assess whether daily duloxetine hydrochloride (duloxetine) decreases average joint pain in women with aromatase inhibitor-associated musculoskeletal syndrome (AIMSS), as measured at 12 weeks by the modified Brief Pain Inventory Short Form (BPI-SF).

Secondary

* To assess whether daily duloxetine decreases worst joint pain in women with AIMSS, as measured at 12 weeks by the modified BPI-SF.
* To assess whether daily duloxetine decreases pain interference in women with AIMSS, as measured at 12 weeks by the modified BPI-SF.
* To investigate whether daily duloxetine improves functioning, pain, and stiffness in the knees/hips according to the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scale. (Exploratory)
* To investigate whether daily duloxetine improves function, pain, and stiffness in the hands according to the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH). (Exploratory)
* To investigate whether daily duloxetine improves functional quality of life as measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES). (Exploratory)
* To investigate whether daily duloxetine improves the proportion of patients reporting changes for the better versus worst as measured by the Global Rating of Change Scale. (Exploratory)
* To investigate whether daily duloxetine decreases analgesic use.
* To investigate whether daily duloxetine increases adherence to, and reduces the discontinuation rate for, aromatase inhibitor (AI) therapy. (Exploratory)
* To assess whether patients receiving duloxetine as compared to placebo have improved depression as measured by the Patient Health Questionnaire (PHQ-9) at Weeks 6 and 12. (Exploratory)
* To explore the relationship between inherited variants in genes responsible for duloxetine metabolism and activity (COMT, HTR3A, SLC6A2, SLC6A4, CYP1A2, CYP2D6) and aromatase (CYP19A1) and change in pain with 12 weeks of treatment. (Exploratory)
* To explore the impact of treatment on serum inflammatory cytokine levels with 12 weeks of treatment at baseline and 12 weeks. (Exploratory)
* To bank blood samples for future correlative analyses. (Exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to baseline pain score (4-6 vs 7-10), and prior taxane use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: 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.
* Arm II: Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91.

Patients complete the modified Brief Pain Inventory Short Form (BPI-SF) questionnaire at baseline and periodically during study treatment. Patients may also complete the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scale, the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES), Global Rating of Change Scale, and the patient Health Questionnaire (PHQ-9).

Patients undergo blood sample collection at baseline and periodically during treatment for correlative studies, including biomarker and genetic studies.

After completion of study treatment, patients are followed up for 168 days.

Arms:
arm 1: 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. arm 2: Patients receive placebo PO QD on days 1-7, BID on days 8-84, and then QD on days 85-91.

Interventions: intervention 1: duloxetine hydrochloride intervention 2: placebo
Intervention descriptions: intervention 1: Given PO intervention 2: Given PO

Protocol document:
Prot_SAP_ICF_000.pdf: 

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December 15, 2017 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
Sandi Jo Hita, Lead Protocol Coordinator (sjhita@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of 
Duloxetine 
for 
Treatment 
of 
Aromatase 
Inhibitor-Associated 
Musculoskeletal Symptoms in Women with Early Stage Breast Cancer.”  
Study Chairs:  Drs. N.L. Henry and A.F. Schott  
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
Study Chair:  Norah Lynn Henry, M.D., Ph.D. 
Phone number:  801/213-6159 
E-mail:  lynn.henry@hci.utah.edu 
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(¥ ) 
Expedited review allowed 
0(025$1'80
The purpose of this memorandum is to inform sites that patients’ unblinded 
treatment assignments are now available for the above-referenced study.   
A report for each follow-up investigator listing the patients for whom you are 
responsible and each patient’s unblinded treatment assignment is available on the 
CRA Workbench of the SWOG website (www.swog.org). A patient-specific report 
providing the patient’s treatment assignment, which you may give to the patient, is 
also available on the CRA Workbench.  
Notifying patients of their blinded intervention assignment may proceed without a 
protocol revision or IRB approval.  Sites may contact their patients to inform them 
of their treatment assignment upon request or per institutional guidelines. 
The results of the 6 trial are available in Henry et al., Journal of Clinical 
Oncology, which was published online on November 14, 2017. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Destin Carlisle – Alliance 
Elliott Lee, Biologics, Inc. 
Becky Fillingham – ECOG-ACRIN 
Mary Bonds – ECOG-ACRIN 





November 1, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
SWOG Operations Offices 
RE: 
Holiday Closure 
0(025$1'80
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(   ) 
Full board review required.  Reason: 
(   ) 
Initial activation (should your institution choose to participate)
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
(  ) No review required 
0(025$1'80
Biologics, Inc. Clinical Trials Services will be closed Thursday, November 26, 2015 and 
Friday November 27, 2015 (in observance of Thanksgiving), Thursday December 24, 
2015 and Friday December 25, 2015 (in observance of Christmas), and Friday January 1, 
2016 (in celebration of the New Year).  
Biologics, Inc. Clinical Trials Services will be open on New Year’s Eve (Thursday 
December 31, 2015). 
Regular business hours are Monday through Friday, 9:00 a.m. - 6:00 p.m. Eastern. Please 
contact 
the 
Biologics 
Clinical 
Research 
Services 
team 
(800/693-4906; 
clinicaltrials@biologicsinc.com) with any questions or concerns. 
This Holiday Closure pertains to the following studies: 
6Lung  
 
 
6Myeloma 
6Genitourinary  
 
6Gastrointestinal 
6Cancer Control   
6Lung 
6Genitourinary  
 
6Gastrointestinal 
6Lung
This memorandum serves to notify the NCI and the SWOG Statistical Center. 
cc: PROTOCOL & INFORMATION OFFICE 
 
Laura Kingsbury, M.R.T. 
Monica Yee 
Amy Johnson 
Stephanie Edwards 
Brian Zeller 
Vicki Green 
Christine McLeod 
Destin Carlisle – Alliance 
Jean Barce 
Elliott Lee, Biologics, Inc. 
Jeri Jardine 
Becky Fillingham – ECOG-ACRIN
Larry Kaye 
Mary Bonds – ECOG-ACRIN 


September 15, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(   ) 
Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The funding memorandum for the above-referenced study has been updated and is located 
on the protocol abstract page of the SWOG website (www.swog.org). 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
Joseph Unger, Ph.D. 
 
Danika Lew, M.A. 
Monica Yee 
Paul Lawson - Lilly 
Elliott Lee – Biologics, Inc. 
ED EFFECTIVE 10/01/2015
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September 15, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry and 
A.F. Schott. 
67$786127,&(
Study Chair:  Norah Lynn Henry, M.D., Ph.D.   
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
IRB Review Requirements 
(   ) 
Full board review required.  Reason: 
(   ) Initial activation (should your institution choose to participate)
(   ) Increased risk to patient
(   ) Complete study redesign 
(   ) Addition of tissue banking requirements
(   ) Study closure due to new risk information 
( ¥ ) 
Expedited review allowed
(   ) 
No review required 
3(50$1(17&/2685(
The above-referenced study has met its accrual goal and will permanently close to accrual 
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This memorandum serves to notify the NCI and the SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Joseph Unger, Ph.D. 
Danika Lew, M.A.
Monica Yee 
3DXO/DZVRQ - Lilly 
Elliott Lee – Biologics, Inc. 
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August 15, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
SWOG Operations Office 
RE: 
Updated Drug Order Form and Holiday Closure 
0(025$1'80
,5%5HYLHZ5HTXLUHPHQWV
(   ) 
Full board review required.  Reason: 
(   ) 
Initial activation (should your institution choose to participate)
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
(  ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. has developed a 
new form for sites to designate non-prescribers to order investigational agent. Please 
note this is an optional form and submission of the form will apply to all studies the 
treating investigator has registered patients on that utilize Biologics Inc. as a distributor. 
This form is available on the protocol abstract page on the SWOG website 
(www.swog.org). The drug order forms for the studies listed below have been updated to 
include this option. 
The Primary Shipping Address and Designee Form pertains to the following studies: 
6 Lung 
6 Myeloma 
6 Genitourinary 
6 Gastrointestinal 
6 Genitourinary 
6 Lung 
6 Lung 
6 Gastrointestinal 
Please also note that Biologics, Inc. Clinical Trials Services will be closed Monday, 
September 7, 2015 in observance of Labor Day. 
Regular business hours will resume on Tuesday, September 8, 2015. Regular business 
hours are Monday through Friday, 9:00 a.m. - 6:00 p.m. Eastern. 
Please contact the Biologics Clinical Research Services team (800/693-4906; 
clinicaltrials@biologicsinc.com) with any questions or concerns. 
This Holiday Closure pertains to the following studies: 
6 Lung 
6 Myeloma 
6 Genitourinary 
6 Gastrointestinal 
6 Cancer Control 
6 Lung 
6 Genitourinary 
6 Gastrointestinal 
6 Lung 
ED
ED 
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D EFFECTIVE 10/01/2015
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August 15, 2015 
 
Memorandum (contd.) 
Page 2 
This memorandum serves to notify the NCI and the SWOG Statistical Center. 
cc: PROTOCOL & INFORMATION OFFICE 
Laura Kingsbury, M.R.T. 
Amy Johnson 
Brian Zeller 
Christine McLeod 
Jean Barce 
Jeri Jardine
Larry Kaye 
Monica Yee 
Stephanie Edwards 
Vicki Green 
Destin Carlisle – Alliance 
Elliott Lee, Biologics, Inc.
Becky Fillingham – ECOG-ACRIN 
Mary Bonds – ECOG-ACRIN
CLOSED EFFECTIVE 10/01/2015


July 1, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
SWOG Operations Office 
RE: 
Updated Drug Order Form and Holiday Closure 
0(025$1'80
,5%5HYLHZ5HTXLUHPHQWV
(   ) 
Full board review required.  Reason: 
(   ) 
Initial activation (should your institution choose to participate)
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
(  ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc has updated all 
SWOG Drug Order Forms to clarify that the  prescriber's signature is required.  
The updated Drug Order Form pertains to the following studies: 
6 (Gastrointestinal) 
6 (Lung 
6 (Gastrointestinal) 
6 (Lung) 
6 (Genitourinary) 
6 (Lung) 
6 (Genitourinary) 
6 (Myeloma) 
Please also note that Biologics, Inc will be closed Friday, July 3, 2015 in observance of 
Independence Day.  Biologics, Inc. will resume regular business hours (M-F, 9-6 ET) on 
Monday July 6, 2015. 
Please contact the Biologics Clinical Research Services team (800/693-4906; 
clinicaltrials@biologicsinc.com) with any questions or concerns. 
ED 
D EFFECTIVE 10/01/2015
BERS 
BERS 
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Memorandum (contd.) 
Page 2 
This Holiday Closure pertains to the following studies: 
6 (Cancer Control – Symptomatic) 
6 (Lung) 
6 (Gastrointestinal) 
6 (Lung) 
6 (Gastrointestinal) 
6 (Lung) 
6 (Genitourinary) 
6 (Lung) 
6 (Genitourinary) 
6 (Myeloma) 
6 (Leukemia) 
This memorandum serves to notify the NCI and the SWOG Statistical Center. 
cc: PROTOCOL & INFORMATION OFFICE 
Mary Alice Norrison - Boehringer Ingelheim 
Laura Kingsbury, M.R.T. 
Linda Fischer - Bristol-Myers Squibb 
 
Tracy Maher, C.C.R.P. 
Becky Fillingham – ECOG-ACRIN 
Amy Johnson 
Laura Gagnon – ECOG-ACRIN 
Austin Hamm. 
Mary Bonds – ECOG-ACRIN 

Brian Zeller 
April Noska – Genentech  
Christine McLeod 
NCI Coop Coverage - Genentech 
Jean Barce 
Leta Truett, Ph.D., M.N. – Janssen Services, LLC 
Jeri Jardine 
Mohan Chelladurai, Ph.D. M.S.A. – 
Larry Kaye 
Janssen Services, LLC
Louise Highleyman 
Royce-Ann Adkins, Janssen Services, LLC 
Monica Yee 
William Heckman - Lilly 
Stephanie Edwards 
Theresa Bucher, R.N., Millennium 
Vicki Green 
Mark Showers – Onyx 
Guadalupe Aquino – Alliance 
Kellis Snodgrass – Pfizer  
Samantha Sublett – Alliance 
Afrouz Bazmi – Quintiles, Inc. 
 
Elliott Lee, Biologics, Inc. 
Steve Shuey – Halozyme Therapeutics
CLOSED EFFECTIVE 10/01/2015
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Myers Squibb 
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Distribution Date: 
June 1, 2015 
E-Mailed Date: 
May 19, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
SWOG Operations Office 
RE: 
Holiday Closure for Monday, May 25, 2015 in Observance of Memorial Day 
0(025$1'80
,5%5HYLHZ5HTXLUHPHQWV
(   ) 
Full board review required.  Reason: 
(   ) 
Initial activation (should your institution choose to participate)
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
(  ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. Clinical Trials 
Services will be closed Monday, May 25, 2015 in observance of Memorial Day. 
Regular business hours will resume on Tuesday, May 26, 2015. Regular business hours 
are Monday through Friday, 9:00 a.m. - 6:00 p.m. Eastern. 
Please contact the Biologics Clinical Research Services team (800/693-4906; 
clinicaltrials@biologicsinc.com) with any questions or concerns. 
This Holiday Closure pertains to the following studies: 
6 (Cancer Control – Symptomatic) 
6 (Lung) 
6 (Gastrointestinal) 
6 (Lung) 
6 (Gastrointestinal) 
6 (Lung) 
6 (Genitourinary) 
6 (Lung)
6 (Genitourinary) 
6 (Myeloma - Active)
6 (Leukemia) 
This memorandum serves to notify the NCI and the SWOG Statistical Center. 
ED EFFECTIVE 10/01/2015
EMBERS 
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Memorandum (contd.) 
Page 2 
cc: PROTOCOL & INFORMATION OFFICE Mary Alice Norrison - Boehringer Ingelheim 
Laura Kingsbury, M.R.T. 
Linda Fischer - Bristol-Myers Squibb 
 
Tracy Maher, C.C.R.P. 
Becky Fillingham – ECOG-ACRIN 

Amy Johnson 
Laura Gagnon – ECOG-ACRIN 
Austin Hamm. 
Mary Bonds – ECOG-ACRIN 
Brian Zeller 
April Noska – Genentech 
 
Christine McLeod 
NCI Coop Coverage - Genentech 
Jean Barce 
Leta Truett, Ph.D., M.N. – Janssen Services, LLC 
Jeri Jardine 
Mohan Chelladurai, Ph.D. M.S.A. – Janssen Services, LLC
Larry Kaye 
Royce-Ann Adkins, Janssen Services, LLC
Louise Highleyman 
William Heckman - Lilly 
Monica Yee 
Theresa Bucher, R.N., Millennium 
Stephanie Edwards 
Mark Showers – Onyx 
Vicki Green 
Kellis Snodgrass – Pfizer 
 
Guadalupe Aquino – Alliance 
Afrouz Bazmi – Quintiles, Inc.  
Samantha Sublett – Alliance 
Steve Shuey – Halozyme Therapeutics 
Elliott Lee, Biologics, Inc. 

CLOSED EFFECTIVE 10/01/2015
vices, LLC 
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Janssen Servi
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February 1, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry and 
A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
IRB Review Requirements 
(   ) 
Full board review required.  Reason: 
(   ) Initial activation (should your institution choose to participate)
(   ) Increased risk to patient
(   ) Complete study redesign 
(   ) Addition of tissue banking requirements
(   ) Study closure due to new risk information 
(   ) 
Expedited review allowed
( ¥ ) 
No review required 
0(025$1'80
The purpose of this memorandum is to inform sites of changes to the Master Forms Set for 
the above-noted study.  
x 
Validated Spanish versions of the following patient completed questionnaires have 
been added: 
o 6Brief Pain Inventory Short Form (BPI-SF) [Cuestionario Breve Para La 
Evaluacion Del Dolor (Edicion Corta)]
o 6 FACT – ES Trial Outcome Index (Version 4) [S1202 FACT – ES (4 
Version)] 
o 6 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) 
Index (Version 3.1) [WOMAC VA3.1 Cuestionario] 
o 6 Modified-Score for the Assessment and Quantification of Chronic 
Rheumatoid Affections of the Hands (M-SACRAH) [Puntuacion-Modificada 
Para la Evaluacion Y Cuantificacion De Afecciones Reumatoides Cronicas De 
Las Manos] 
o 6 Global Ratings of Change in Joint Pain and Stiffness [Valoraciones 
Globales De Cambio En Dolor Y Rigidez En Las Articulaciones] 
o 6Patient Health Questionnaire-9 (PHQ-9) [Cuestionario Sobre La Salud 
Del Paciente-9 (PHQ-9)] 
ED EFFECTIVE 10/01/2015
U 
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Duloxetine fo
Duloxetine
tal Symptoms
tal Symptoms
Drs. N.L. Henr
s. N.L. Hen
d.  Reason: 
d.  Reason: 
should your
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f tissue bankin
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S1202 
Memorandum (contd.)
Page 2 
o 6Patient Treatment Satisfaction Form [Formulario De Satisfaccion Con El
Tratamiento Del Paciente] 
x
6 
Cover 
Sheet 
for 
Patient-Completed 
Questionnaires: 
“Language
questionnaire(s) Fompleted in [ ] English [ ] Spanish has been added. 
This memorandum serves to notify the NCI and the SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Danika Lew, M.A. 
Monica Yee 
William Heckman - Lilly 
Elliott Lee – Biologics, Inc. 
CLOSED EFFECTIVE 10/01/2015


Distribution Date: 
February 1, 2015 
DCP Submission Date: 
January 19, 2015 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
5(9,6,21
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
( ¥ ) Expedited review allowed 
(   ) 
No review required 
5(9,6,21
The above-referenced study has been updated as follows: 
1. 
Title Page, Page 1: The Version Date of the protocol and Model Consent Form 
have been updated. Lisa Hansen has been removed as the Nurse Coordinator. 
NCIC CTG has been removed from the Participants table. 
2. 
Table of Contents, Page 3: The Table of Contents have been updated. 
3. 
Section 3.1f.4, Page 16: The first sentence has been revised from “…drugs received 
using the SWOG Blinded Drug Accountability Record available on the 6 abstract 
page on the SWOG website (http://www.swog.org).” to “…drugs received using the 
Investigational Agent Accountability Record for Oral Agents (Oral DARF). The Oral 
DARF can be found on the NCI home page (http://ctep.cancer.gov).” The 
Pharmaceutical Management Branch has created an NCI Investigational Agent 
Accountability Record for Oral Agents (Oral DARF). Use of the Oral DARF became 
mandatory effective March 1, 2014. Effective immediately, all QHZshipments of oral 
agents on SWOG and CTSU studies must be recorded on this Oral DARF which is 
available on the NCI home page (http://ctep.cancer.gov). Any current inventory of 
oral agents must also be transferred to the new form. An audit deficiency for failure to 
implement the new Oral DARF will not be given prior to the date of this notification. 
ED 
D EFFECTIVE 10/01/2015
g.org) 
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3


S1202 
 
Revision #5 (contd.) 
Page 2 
4. 
Section 5.2a.4, Page 19: This criterion has been added to include patients on 
LHRH agonist therapy with estradiol levels consistent with institutional normal 
values for post-menopausal status. 
5. 
Section 5.2h, Page 20: “…or while on protocol treatment” has been added to the 
end of the second sentence for clarification. “Aspirin is permitted (see Section 
8.2).” has been added for clarification. 
6. 
Section 5.2k, Page 20: “was not taken concurrently with AI therapy and” was 
removed from the last sentence as it is a barrier to accrual. Most patients take 
venlafaxine for treatment of depression or hot flashes and not for pain. There have 
been several patients who were taking venlafaxine for hot flashes while they were 
taking an AI, but stopped venlafaxine because the hot flashes improved. These 
patients are now experiencing pain while taking the AI and would like to enroll in 
the trial, but are unable to due to this criterion.  
7. 
Section 5.2m, Page 21: “or Spanish” has been added as validated Spanish 
questionnaires are now available.  
8. 
Section 7.2a, Page 22: The following sentence has been added to the 4th
paragraph for clarification: “Bottle #1 and #2 are dispensed at this visit.”. 
9. 
Section 7.2b, Page 23: The following sentence has been added as the last 
sentence in the 9th paragraph for clarification: “She is permitted to start this at any 
time following completion of the taper of the study drug (Day 92).”. 
10. 
Section 9.0, Page 28: The header, including required studies and timepoints in 
weeks and days, has been added to the top of this page. 
11. 
Section 15.1a, Page 40: The following note was added to this section for 
clarification: “** With patient consent, leftover specimens will be banked for future 
unknown use.” 
12. 
Section 15.2c.4, Page 41:  Dr. Carol Moinpour and Lisa Hansen have been 
replaced with Dr. Henry and the SWOG Data Operations Office. 
13. 
Section 16.1f, Page 44: The section regarding the reporting of pregnancy, fetal 
death, and death neonatal has been removed as it is not applicable for this patient 
population of post-menopausal women. The pre-existing Page 44 has been 
removed and subsequent pages have been repaginated. 
Institutions PXVW update their local consent forms to include the change to the 
Model Consent Form. SWOG considers that the Model Consent Form change 
GRHVQRW represent an alteration in risk/benefit ratio. Therefore, local accrual does 
QRW need to be suspended pending implementation of this change. Patients need 
not be informed of the following changes unless required by the local IRB. 
14. 
Model Consent Form, Page 9:  Under “Will my medical information…”, Alliance, 
ECOG-ACRIN, and NRG have been added to the bulleted list. 
15. 
Model Consent Form, Page 10:  Under “What are the costs…”, the link to the 
insurance coverage website has been updated in the 6th paragraph. 
16. 
Model Consent Form, Page 14: Under the Participant signature line: “(or legally 
authorized representative)” has been removed. 
CLOSED EFFECTIVE 10/01/2015
the 
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S1202 
 
Revision #5 (contd.) 
Page 3 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
Joseph Unger, Ph.D. 
 
Danika Lew, M.A. 
Monica Yee 
William Heckman - Lilly 
Elliott Lee – Biologics, Inc. 
CLOSED EFFECTIVE 10/01/2015


December 15, 2014 
TO: 
ALL 
SWOG 
MEMBERS, 
CCOP 
AND 
AFFILIATE 
MEDICAL 
ONCOLOGISTS AND PATHOLOGISTS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org)  
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine 
for 
Treatment 
of 
Aromatase 
Inhibitor-Associated 
Musculoskeletal 
Symptoms in Women with Early Stage Breast Cancer.” Study Chairs:  
Drs. N.L. Henry and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(   ) 
Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. Clinical Trials 
Services will be closed Wednesday, December 24, 2014, Thursday, December 25, 
2014, and Thursday, January 1, 2015, in observance of the seasonal holidays. 
Regular business hours will continue on December 26 and January 2 from 9:00 a.m. – 
6:00 p.m. Eastern. 
If you have questions or need to coordinate shipments in advance, please contact 
your Clinical Research Services team at 800/693-4906 or via e-mail at 
clinicaltrials@biologicsinc.com.
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Monica Yee 
 
Joseph Unger, Ph.D. 
Paul Lawson - Lilly 
 
Danika Lew, M.A. 
Elliott Lee – Biologics, Inc. 
D EF
EFF
¥
FFECTIVE 10/01/2015
ICAL 
CAL 
@swog.org)  
@swog.org)  
udy of Duloxe
dy of Duloxe
d 
Musculos
Musculos
ancer.” Study
ancer.” Stud
Ph.D.   
D.    
quired. Reaso
quired. Reaso
ation
ation (should y
(should
ed risk to pati
ed risk to p
plete study re
lete study re
ddition of tissu
ddition of tiss
Study closure
Study closure
Expedited revi
Expedited revi
 ) No review
 ) No revi
EF
purpose of
purpos
he p
ces will
ces w
Servi
, and 
, and
2014
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6:0



November 1, 2014 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(    ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
 (    ) Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. Clinical Trials 
Services will be closed Thursday, November 27 and Friday, November 28, 2014 in 
observance of the Thanksgiving holiday. 
Regular business hours will resume on Monday, December 1, 2014.  Regular business 
hours are Monday through Friday, 9:00 a.m. – 6:00 p.m. Eastern. 
For additional information, please access Biologics’ website at www.biologicsinc.com.
If you have questions or need to coordinate shipments in advance, please contact your 
Clinical 
Trial 
Project 
Manager 
at 
800/693-4906 
or 
via 
email 
at 
clinicaltrials@biologicsinc.com. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
 
Joseph Unger, Ph.D. 
 
 
Danika Lew, M.A. 
 
Monica Yee 
ED EFFECTIVE 10/01/2015
ISTS
ST
y of Duloxetine
f Duloxetin
keletal Sympt
eletal Sympt
airs:    Drs. N
irs:    Drs. N
h.D.   
D.  
quired. Reason
uired. Reason
tion (should yo
ion (should y
 risk to patien
risk to patie
ete study rede
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on of tissue b
udy closure du
udy closure 
pedited review
pedited revie
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FF
purpose of th
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F


August 15, 2014 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
IRB Review Requirements 
(   ) 
Full board review required.  Reason: 
(   ) Initial activation (should your institution choose to participate)
(   ) Increased risk to patient
(   ) Complete study redesign 
(   ) Addition of tissue banking requirements
(   ) Study closure due to new risk information 
(   ) 
Expedited review allowed
( ¥ ) 
No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. Clinical Trials 
Services will be closed Monday, September 1, 2014, in observance of Labor Day. 
Regular business hours will resume on Tuesday, September 2, 2014. Regular business 
hours are Monday through Friday, 9:00 a.m. - 6:00 p.m. Eastern. 
Please contact the Biologics Clinical Research Services team (800/693-4906; 
clinicaltrials@biologicsinc.com)  with any questions or concerns. 
This memorandum serves to notify the NCI and the SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Jo Ann Hartline, M.P.H., M.S.W. 
Joseph Unger, Ph.D. 
William Heckman - Lilly 
Danika Lew, M.A. 
Elliott Lee – Biologics, Inc. 
Monica Yee 
 
ED EFFECTIVE 10/01/2015
S; CTSU 
; CTS
@swog.org) 
@swog.org) 
dy of Duloxet
dy of Duloxet
oskeletal Sym
eletal Sy
hairs:    Drs. 
airs:    Drs
Ph.D.   
D.    
required.  Re
required.  R
vation (should
vation (shou
ed risk to patie
ed risk to pati
plete study red
plete study re
ddition of tissu
dition of tis
Study closure
Study closure
Expedited rev
Expedited rev
 ) 
No review
) 
No rev
EF
purpose of
purpose of
e p
ces will b
ces w
Servi
ular 
ular 
Regu
s
hours
P


June 15, 2014 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
IRB Review Requirements 
(   ) 
Full board review required.  Reason: 
(   ) Initial activation (should your institution choose to participate)
(   ) Increased risk to patient
(   ) Complete study redesign 
(   ) Addition of tissue banking requirements
(   ) Study closure due to new risk information 
(   ) 
Expedited review allowed
( ¥ ) 
No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. Clinical Trials 
Services will be closed Friday, July 4, 2014 in observance of Independence Day. 
Regular business hours will resume on Monday, July 7, 2014.  Regular business hours 
are Monday through Friday, 9:00 a.m. - 6:00 p.m. Eastern. 
Please contact the Biologics Clinical Research Services team (800/693-4906; 
clinicaltrials@biologicsinc.com) with any questions or concerns. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Monica Yee 
William Barlow, Ph.D. 
Jo Ann Hartline, M.P.H., M.S.W. 
Joseph Unger, Ph.D. 
William Heckman - Lilly 
Danika Lew, M.A. 
Elliott Lee – Biologics, Inc. 
ED 
D EFFECTIVE 10/01/2015
CTSU 
SU 
wog.org) 
wog.org
of Duloxetine
f Duloxetin
keletal Sympto
eletal Sympto
rs:    Drs. N.
   Drs. N
.D.   
D. 
quired.  Reaso
quired.  Reas
ion (should yo
ion (should y
risk to patient
risk to patie
ete study redes
te study rede
tion of tissue b
on of tissue 
udy closure du
udy closure
xpedited review
pedited revi
No review r
No review r
FF
purpose of th
purpose of th
ces will be 
ces will be 
ervi
ular bu
ular bu
Regu
Mond
Mon
are M
Ple
c


May 15, 2014 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
IRB Review Requirements 
(   ) 
Full board review required.  Reason: 
(   ) Initial activation (should your institution choose to participate)
(   ) Increased risk to patient
(   ) Complete study redesign 
(   ) Addition of tissue banking requirements
(   ) Study closure due to new risk information 
(   ) 
Expedited review allowed
( ¥ ) 
No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. Clinical Trials 
Services will be closed Monday, May 26, 2014 in observance of Memorial Day.   
Regular business hours will resume on Tuesday, May 27, 2014.  Regular business hours 
are Monday through Friday, 9:00 a.m. - 6:00 p.m. Eastern. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
William Barlow, Ph.D. 
Joseph Unger, Ph.D. 
 
Danika Lew, M.A. 
 
Monica Yee 
 
Jo Ann Hartline, M.P.H., M.S.W. 
William Heckman - Lilly 
Elliott Lee – Biologics, Inc. 
ED EFFECTIVE 10/01/2015
OGISTS
STS
@swog.org) 
@swog.org) 
dy of Duloxet
dy of Duloxet
oskeletal Sym
eletal Sy
hairs:    Drs. 
airs:    Drs
Ph.D.   
D.    
required.  Re
required.  R
vation (should
vation (shou
ed risk to patie
ed risk to pati
plete study red
plete study re
ddition of tissu
dition of tis
Study closure
Study closure
Expedited rev
Expedited rev
 ) 
No review
) 
No rev
EF
purpose of
purpose of
e p
ces will b
ces w
Servi
ular 
ular 
Regu
Mo
M
are M
T


Distribution Date: 
May 15, 2014 
DCP Submission Date: 
April 29, 2014 
TO: 
ALL NATIONAL CLINICAL TRIALS NETWORK (NCTN) MEMBERS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator (E-mail:  kkaberle@swog.org) 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
5(9,6,21
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
( ¥ ) Expedited review allowed 
(   ) 
No review required 
5(9,6,21
The above-referenced study has been updated as follows: 
1. 
The Version Date of the protocol and Model Consent Form have been updated. 
2. 
Title Page, Page 1: The participants list has been revised to the new NCI approved 
format. Joseph Unger’s degree has been updated from “M.S.” to “Ph.D.”. 
3. 
Table of Contents, Pages 2-3:  The Table of Contents has been updated. 
4. 
Section 5.2h, Page 20: The following eligibility criterion has been revised from 
“Patients must not be taking any contraindicated medications listed on the 
duloxetine package insert including the following: treatment with phenothiazines, 
propafenone, flecainide, or linezolid; treatment with MAO-Inhibitor within 14 days 
prior to registration; current use of anticoagulation medication (e.g., heparin, 
warfarin).” to “Patients must not take MAO-Inhibitors for 14 days before registration 
or any time during study treatment. Concomitant therapy with heparin and warfarin 
is also not permitted at registration.” for clarification purposes.  
ED EFFECTIVE 10/01/2015
wog.org) 
wog.org
of Duloxetine
f Duloxetin
keletal Sympto
eletal Sympto
rs:    Drs. N.
   Drs. N
.D.   
D. 
red. Reason:
ed. Reason:
on (should yo
on (should y
risk to patient
risk to patie
te study redes
te study redes
ion of tissue b
on of tissue b
udy closure du
udy closure 
pedited review 
edited revie
No review re
No review re
FF
above-referen
above-referen
The V
Th
1.
T
2.
3


S1202 
 
Revision #4 (contd.) 
Page 2 
5. 
Section 5.2n, Page 21: “Patients with osteoarthritis are eligible.” was added to the 
end of this eligibility criterion for clarification. 
6. 
Section 5.4a, Page 21: “or their legally authorized representative” was added after 
“All patients” per new SWOG standard language. 
7. 
Section 8.2, Page 25: The third paragraph was added to provide clarification to 
treating investigators that caution should be taken if patients take aspirin or non-
steroidal anti-inflammatory drugs while on study. The following was added to the 
fourth paragraph to include additional specific drugs that increase risk of serotonin 
syndrome with duloxetine: “tramadol, linezolid, or other serotonergic medications”. 
“Triptans” was replaced with “these medications”. A note regarding concomitant use 
of heparin and warfarin was added at the end of this section.  Information from Page 
25 has been displaced to Page 26. 
8. 
Section 8.5, Page 26: The reference to “AdEERS” has been changed to “CTEP-
AERS”.
9. 
Section 9.0, Page 28: An X has been added on the “Dispense blinded study drug” 
during Week 12 for clarification that sites should dispense bottle #3 during this visit.  
10. 
Section 16.1b, Pages 42-43: The reference to the “NCI’s Adverse Event Expedited 
Reporting System (AdEERS)” has been changed to “CTEP Adverse Event 
Reporting System (CTEP-AERS)” in this section. The link for NCI guidelines for 
CTEP-AERS has been updated. The sentence regarding paper forms being 
removed from the website and no longer accepted has been removed. 
11. 
Section 16.1e, Page 43: References to “AdEERS” have been changed to “CTEP-
AERS” throughout this section.  
12. 
Section 16.1f, Page 44: This section regarding reporting pregnancy, fetal death, and 
death neonatal has been added as it is a new SWOG standard section. Subsequent 
pages have been renumbered accordingly. 
Institutions PXVW update their local consent forms to include the changes to the Model 
Consent Form within 90 days of distribution of this notice. SWOG considers that the Model 
Consent Form changes GRQRW represent an alteration in risk/benefit ratio.  Therefore, local 
accrual does QRW need to be suspended pending implementation of these changes. Patients 
currently receiving duloxetine/placebo and patients who sign a consent form prior to local 
implementation of the consent form changes PXVW be informed of the following changes.  
The manner by which this notification takes place is at the discretion of the local institution.  
At a minimum, the patient must be notified by the next visit and this notification process must 
be documented in the patient chart. 
13. 
Model Consent Form, Page 8: A new paragraph regarding not using MAO-Inhibitors, 
heparin and warfarin was added for patient’s information. Additional information 
regarding a possible increase in bleeding risk was included in this paragraph for 
patients who take aspirin and NSAIDs while on study. 
14. 
Model Consent Form, Page 11: An italicized paragraph beginning with “NOTE: Use 
the following types of format…” has been deleted as it was inadvertently left in the 
consent form.  
15. 
Model Consent Form, Page 14: “(or legally authorized representative)” was added 
beneath the participant signature line as it is now a SWOG standard item.  
cation to 
ation to
rin or non-
or non-
added to the 
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this sect
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3: References
3: References
s section.  
 section
age 44: This s
age 44: This s
al has been ad
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e been renumb
 been renumb
XVW
VW update th
 update 
rm within 90 d
rm within 90 d
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 nee
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mplementation 
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The manner 
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13. 
13.


S1202 
 
Revision #4 (contd.) 
Page 3 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
William Barlow, Ph.D. 
 
Joseph Unger, Ph.D. 
 
Danika Lew, M.A. 
Monica Yee 
Jo Ann Hartline, M.P.H., M.S.W. 
William Heckman - Lilly 
Elliott Lee – Biologics, Inc. 
CLOSED EFFECTIVE 10/01/2015


March 1, 2014 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
( ¥ ) Expedited review allowed (if your site decides to distribute materials) 
( ¥ ) No review required (if your site does not decide to distribute materials) 
0(025$1'80
A sample brochure and flier for recruitment to 6 have been posted to the study 
guidelines page on the SWOG website (www.swog.org).
If your institution would like to use these materials, you may add your contact information 
on the documents and must submit the materials to your local Institutional Review Board 
(IRB) for approval prior to distribution. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Jo Ann Hartline, M.P.H., M.S.W. 
William Barlow, Ph.D. 
William Heckaman-Lilly Pharmaceuticals 
Joseph Unger, M.S. 
Elliott Lee - Biologics inc. 
Danika Lew, M.A. 
Emily Demske - CTSU 
Monica Yee 
 
ED EFFECTIVE 10/01/2015
COLOGISTS
OLOGIST
II Study of Du
 Study of D
sculoskeletal 
culoskele
dy Chairs:    
dy Chairs:    
M.D., Ph.D.   
.D., Ph
du 
QWV
QWV
w required. Re
w required. Re
activation (sh
activation (sh
reased risk to
reased risk
Complete stud
Complete stud
Addition of t
Addition o
 ) 
Study clo
 ) 
Study clo
 ) Expedited
) Expedi
( ¥ ) No re
 ) No
E
mple 
mple 
A sam
eline
eline
guide
If yo
o


Distribution Date: 
February 1, 2014 
DCP Submission Date: 
January 23, 2014 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
5(9,6,21
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
( ¥ ) Expedited review allowed 
(   ) 
No review required 
5(9,6,21
The above-referenced study has been updated as follows: 
1. 
Title page, Page 1: The version date has been updated. The NCT number has 
been added below the title. 
2. 
Section 3.1f.3, Pages 14-16: The first paragraph has been divided into three 
sections. “SWOG Institutions” has been added as the first section. “Non-SWOG 
Institutions” has been added as the second section with instructions for sending 
institution contact information to the distributor. “All Institutions” has been added 
as the third section. These changes have been made to clarify the drug ordering 
process for SWOG institutions and non-SWOG institutions. 
ED E
D EFFECTIVE 10/01/2015
ONCOLOGIST
ONCOLOGIST
se III Study of 
III Study 
Musculoskele
Musculoskele
Study Chairs: 
dy Chairs
y, M.D., Ph.D. 
M.D., Ph.D
 
h.edu 
h.edu 
PHQWV
PHQWV
view required.
ew required
tial activation 
tial activatio
Increased risk
Increased risk
Complete s
Complete
  ) 
Addition 
  ) 
Addition 
(   ) 
Study 
(   ) 
Study
( ¥ ) Expedi
) Exped
(   ) 
No
(   ) 
N
D E
abo
ab
The a
1.


S1202 
 
Revision #3 (contd.) 
Page 2 
3. 
Section 5.2k, Page 20:  The following sentence has been bolded in order to 
reduce ineligibility:  “Patients must not have previously taken the serotonin 
norepinephrine reuptake inhibitors (SNRI) duloxetine or milnacipran.” The 
spelling of norepinephrine has been corrected. 
Institutions PXVW update their local consent forms to include the changes to the Model 
Consent Form within 90 days of distribution of this notice.  SWOG considers that the 
Model Consent Form changes GR QRW represent an alteration in risk/benefit ratio.  
Therefore, local accrual does QRW need to be suspended pending implementation of 
these changes. Patients need not be informed of the following changes unless required 
by the local IRB. 
4. 
Model Consent Form, Page 7: Under “Likely”, vomiting, constipation, diarrhea, 
dizziness, decreased appetite, and increased sweating have been moved under 
“Less Likely” to be consistent with the adverse events listed in Section 3.1c. The 
heading of “likely” has been corrected from “…more than 5% of patients” to 
“…more than 10% of patients”. “(Occurring in 1-10% of patients)” was added to 
the “Less Likely” heading. 
5. 
Model Consent Form, Page 8: “(Occurring in less than 1% of patients)” was 
added to the Rare but serious heading in order to be consistent with the adverse 
events listed in Section 3.1c. 
Please attach this memorandum to your copy of the protocol.  Replacement pages are 
attached for the revised pages referenced above. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
William Barlow, Ph.D. 
Joseph Unger, M.S. 
 
Danika Lew, M.A. 
 
Monica Yee 
 
Jo Ann Hartline, M.P.H., M.S.W. 
CLOSED EFFECTIV
y t
TIVE 10/01/2015
del 
el
at the 
th
fit ratio.  
atio.  
entation of 
ntation of 
ess required 
ess require
nstipation, dia
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ave been mov
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sted in Sectio
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re than 5% o
than 5%
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0% of patients
g in less than
less than
 order to be c
order to be 
copy of the p
of the p
ed above.
ed above.
he NCI and 
he NCI an
ORMATION O
ORMATION
Ph.D. 
Ph.D. 
r, M.S.
, M.S.
w, M.A.
w, M.A.
ee 
ee 
n Hartline, M.P
n Hartline, M


December 15, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:  Drs. N.L. Henry and 
A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(   ) 
Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites that Biologics, Inc. Clinical Trials 
Services will be closed Tuesday, December 24, 2013, Wednesday, December 25, 2013, 
and Wednesday, January 1, 2014, in observance of the seasonal holidays. 
Regular business hours will continue December 26-27 and December 30-31 from 9:00 
a.m. – 6:00 p.m. Eastern. 
If you have questions or need to coordinate shipments in advance, please contact your 
Clinical 
Research 
Services 
team 
at 
800/693-4906 
or 
via 
e-mail 
at 
clinicaltrials@biologicsinc.com.
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
William Barlow, Ph.D. 
Joseph Unger, M.S. 
 
Danika Lew, M.A. 
 
Monica Yee 
 
Jo Ann Hartline, M.P.H., M.S.W. 
ED 
D EFFECTIVE 10/01/2015
TS 
f Duloxetine fo
f Duloxetine f
etal Symptom
al Symptom
Drs. N.L. Hen
Drs. N.L. Hen
    
. Reason:
eason: 
(should your in
(should your i
k to patient
k to patient
study redesign
study redes
n of tissue ban
of tissue ban
y closure due t
closure due 
ited review all
ited review al
No review requ
o review requ
FF
rpose of this 
ose of this 
ces will be clo
ces will be cl
Wednesday
Wednesday
d W
ular bu
ular bu
Regu
– 6:
– 6
a.m. –
If y
C


Distribution Date: 
December 15, 2013 
DCP Submission Date: 
November 22, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
5(9,6,21
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) 
Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
( ¥ ) Expedited review allowed 
(   ) 
No review required 
5(9,6,21
The above-referenced study has been updated as follows: 
1. 
Title Page, Page 1: The version date has been updated. Study Coordinator has 
been updated to Study Chair.  This change has also been made in Sections 
3.1c.4 (Page 14) and 8.5 (Page 26). 
2. 
Section 5.2a.3, Page 19:  “unless  60 years of age” has been added in order to 
not require a non-standard of care blood draw and FSH lab test in women 60 
years old and older. 
3. 
Section 5.2b, Page 19: Initial start of AI therapy has been changed from “no more 
than 12 months prior to registration” to “no more than 36 months prior to 
registration” in order to allow more patients to be eligible for this study.  The limit 
of 12 months since AI treatment initiation has shown to be too restrictive for 
patients who have tried multiple aromatase inhibitor medications before 
considering enrollment in this trial. 
ED EFFECTIVE 10/01/2015
OGISTS
STS
udy of Duloxe
dy of Duloxe
oskeletal Sym
oskeletal Sy
Chairs:    Drs. 
Chairs:    Drs
Ph.D.   
D.    
eview required
eview required
nitial activation
itial activatio
participate) 
participate
eased risk to p
ased risk to p
omplete study 
omplete stud
Addition of tis
Addition of tis
Study closu
Study clos
Expedited re
Expedited r
(   ) 
No rev
(   ) 
No rev
EF
above-re
above-
The a
1.


S1202 
 
Revision #2 (contd.) 
Page 2 
4. 
Section 9.0, Pages 27 and 29: The “~” footnote has been added in the boxes for 
pre-study history and pre-study physical exam on Page 27. On Page 29, the “~” 
has been added and defined as “Must be performed within 28 days prior to 
registration.” 
5. 
Section 14.4b, Page 37: “Institutional surgical pathology report to confirm 
diagnosis of ER/PgR status” has been added as it was inadvertently missing 
previously. 
6. 
Section 16.0, Pages 42-43: SWOG’s standard confidentiality statement has been 
added above Section 16.1. The second paragraph in Section 16.1b has been 
displaced to the next page. 
No changes have been made to the Model Consent Form; its Version Date remains 
9/18/13. 
Please attach this memorandum to your copy of the protocol.  Replacement pages are 
attached for the revised pages referenced above. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
William Barlow, Ph.D. 
Joseph Unger, M.S. 
 
Danika Lew, M.A. 
 
Monica Yee 
 
Jo Ann Hartline, M.P.H., M.S.W. 
CLOSED EFFECTIVE 10/01/2015
rm 
m 
ssing 
sin
ent has been
ent has bee
6.1b has bee
6.1b has bee
Version Date
Version Dat
ocol.  Replace
ocol.  Replace
OG Statistical
Statistical
ICE 
CE 
 M.S.W.
 M.S.W.


November 1, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(    ) 
Full board review required. Reason: 
(    ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites of a holiday closure of Biologics, Inc.  
Biologics, Inc. Clinical Trials Services is closed Thursday, November 28 and Friday, 
November 29, 2013 in observance of the Thanksgiving holiday. 
Regular business hours will resume on Monday, December 2, 2013.  Regular business 
hours are Monday through Friday, 9:00 a.m. – 6:00 p.m. Eastern. 
For additional information, please access Biologics’ website at www.biologicsinc.com.
If you have questions or need to coordinate shipments in advance, please contact your 
Clinical Trial Project Manager at 800/693-4906. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Danika Lew, M.A. 
 
William Barlow, Ph.D. 
Monica Yee 
Joseph Unger, M.S. 
Jo Ann Hartline, M.P.H., M.S.W. 
D 
D EF
EFFECTIVE 10/01/2015
ISTS
ST
y of Duloxetine
f Duloxetin
keletal Sympt
eletal Sympt
airs:    Drs. N
irs:    Drs. N
h.D.   
D.  
ew required. R
ew required. R
al activation (s
al activation (s
articipate) 
articipate) 
ed risk to pati
ed risk to p
plete study re
lete study re
ddition of tissu
ddition of tiss
Study closure
Study closure
Expedited revi
Expedited revi
¥ ) No review
 ) No revi
EF
purpose of
purpos
he p
gics, In
gics, 
Biolog
ember
mbe
Nov
Regu
h


Distribution Date: 
November 1, 2013 
DCP Submission Date: 
September 18, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS; CTSU 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Coordinators:    Drs. N.L. 
Henry and A.F. Schott. 
5(9,6,21
Study Coordinator:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(   ) 
Full board review required. Reason: 
(   ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
( ¥ ) Expedited review allowed 
(   ) 
No review required 
5(9,6,21
Institutions PXVW update their local consent forms to include the changes to the Model 
Consent Form.  
SWOG considers that the Model Consent Form changes GRQRW represent an alteration 
in risk-benefit ratio.  Therefore, local accrual does QRW need to be suspended pending 
implementation of these changes. 
Patients currently on treatment need not be informed of these changes unless required 
by the local Institutional Review Board (IRB). 
ED EFFECTIVE 10/01/2015
COLOGISTS
COLOGIST
hase III Study 
ase III Study 
ed Musculoske
Musculos
. Study Coor
Study Coo
ynn Henry, M.D
nn Henry, M.D
991 
991 
mich.edu
mich.edu
UHPHQWV
UHPHQWV
ull board review
ull board revi
(   ) 
Initial
(   ) 
Initial
pa
pa
  ) 
Increase
  ) 
Increase
(   ) 
Comp
(   ) 
Comp
(   ) 
Add
  ) 
A
(   ) 
S
(  
( ¥ ) Ex
E
(   )
ED
I


S1202 
 
Revision #1 (contd.) 
Page 2 
The above-referenced study has been updated as follows: 
1. 
Title Pages, Pages 1-3: The title pages have been reformatted to the new SWOG 
standard. CTSU has been added to the Participant’s list. The version date has 
been updated. 
2. 
CTSU Information, Page 4:  This page has been added to include CTSU 
information. Subsequent pages have been renumbered accordingly. 
3. 
Section 3.1e, Page 14: The temperature storage instructions have been revised 
from “25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP 
Controlled Room Temperature]” to “(15°C to 25°C). Do not refrigerate or freeze.” 
in order to be consistent with Section 3.2c. 
4. 
Section 5.1a, Page 19:  “(Stage I-III)” has been added to clarify which stage 
patients are eligible. 
5. 
Section 5.2b, Page 19: In the first sentence “but no longer than 12 months” has 
been removed. The following sentence has been added for additional clarification 
regarding prior and current AI therapy: “Patients may have received any number 
of prior AI therapies, but the first AI therapy must have started no more than 12 
months prior to registration.” 
6. 
Section 7.7, Page 24: This section has been added to include information 
regarding non-emergency unblinding once all patients have completed follow-up. 
7. 
Section 9.0, Page 28: The 6 Patient Treatment Satisfaction Form has been 
added to the calendar under Week 12 as this form has been added to the protocol 
and Section 14.4e. The “X” on Day 43 for dispensing study drug has been 
removed as all drug is dispensed on Day 1. 
8. 
Section 13.2, Pages 34-36:  This section has been added to include CTSU 
registration information.  Subsequent sections have been renumbered 
accordingly. An affected section reference was updated on Page 21, Section 5.4b. 
9. 
Section 13.3e, Pages 34-35: This section has been added because Cooperative 
Group Credit must be assigned for CTSU registration.  Subsequent sections have 
been renumbered accordingly. 
10. 
Section 14.3c, Page 37: This section has been added to reference the CTSU 
Participation Table on Page 4 for more information. 
11. 
Section 14.4e, Pages 38-39: This section has been added to include submission 
of the 6 Patient Treatment Satisfaction Form within 14 days of the Day 85 
assessment. Subsequent sections have been renumbered accordingly. Affected 
section references were updated on Page 24, Section 7.4 and Page 39, Section 
14.4.
12. 
Section 18.3, Page 53: Anne F. Schott, M.D. and her contact information have 
been replaced with those of Craig R. Nichols, M.D. as Dr. Schott is no longer the 
SWOG Executive Officer for this protocol. 
13. 
Model Consent Form, Page 9:  Under “Will my medical information be kept 
private?”, the Cancer Trials Support Unit (CTSU) has been added to the list of 
organizations that may look at medical records. 
CLOSED EFFECTIVE 10/01/2015
CTSU 
CTSU 
 been revised
been revis
6°F) [see U
6°F) [see U
frigerate or fre
erate or fr
ded to clarify 
ded to clarify
ut no longer t
ut no longer
been added fo
en added fo
atients may h
ts may
erapy must ha
erapy must ha
ectio
ecti n has b
 has b
linding once a
linding once
he 
e 6
6
CT
Pati
Pa
under Week 1
under Week
The “X” on 
The “X” on 
ug is dispense
ug is dispens
2, Pages 34-3
2, Pages 34-
n information
information
ngly. An affect
ngly. An a
ection 13.3e, P
ection 13.3
Group Credit 
roup Credit 
been renum
en renum
10. 
Sectio
10. 
Se
Par
Pa
11. 
11. 


S1202 
 
Revision #1 (contd.) 
Page 3 
In addition to the protocol revisions above, the form packet, located on the protocol 
abstract page on the SWOG website (www.swog.org), has been revised with the following 
changes: 
x
6 Onstudy Form (Form #62636): Questions were updated about other 
treatment on the bottom of Page 1 to match eligibility requirements in Section 5.0 
of the protocol. 
x
6 Cover Sheet for Patient-Completed Questionnaires (Form #54672): The 
6 Patient Treatment Satisfaction Form was added. 
x
6 Patient Treatment Satisfaction Form (Form #37300): This form has been 
added to the forms packet as it was inadvertently missing previously. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
William Barlow, Ph.D. 
Joseph Unger, M.S. 
 
Danika Lew, M.A. 
 
Monica Yee 
 
Jo Ann Hartline, M.P.H., M.S.W. 
CLOSED EFFECTIVE 10/01/2015
er 
er 
5.0 
.0
72): The 
72): The 
orm has been
orm has be
sly. 
sly. 
nter.
er


October 15, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(    ) 
Full board review required. Reason: 
(    ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to request that sites with registered currently 
patients and patients registered in the future submit the pre-registration pathology report 
to the SWOG Data Operations Center by uploading the report via Medidata Rave® on 
the Source Documentation page. Data submission procedures are located in Section 
14.3 of the protocol. The pre-registration pathology report will be added to Section 14.4b 
in a future amendment. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
 
William Barlow, Ph.D. 
 
Joseph Unger, M.S. 
 
Danika Lew, M.A. 
Monica Yee 
Jo Ann Hartline, M.P.H., M.S.W. 
ED EF
EFFECTIVE 10/01/2015
ISTS
ST
y of Duloxetine
f Duloxetin
keletal Sympt
eletal Sympt
airs:    Drs. N
irs:    Drs. N
h.D.   
D.  
ew required. R
ew required. R
al activation (s
al activation (s
articipate) 
articipate) 
ed risk to pati
ed risk to p
plete study re
lete study re
ddition of tissu
ddition of tiss
Study closure
Study closure
Expedited revi
Expedited revi
¥ ) No review
 ) No revi
EF
purpose o
purpo
he 
nts and 
nts an
patien
e SW
e SW
to the
Sou
So
the S
14.3 
in


August 15, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(    ) 
Full board review required. Reason: 
(    ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites of the Holiday closure of Biologics, 
Inc. Biologics, Inc. Clinical Trial Services is FORVHG 0RQGD\ 6HSWHPEHU   in
observance of the Labor Day holiday. 
Regular business hours are Monday through Friday, 9:00 a.m. – 6:00 p.m. Eastern. 
For 
additional 
information, 
please 
access 
Biologics’ 
new 
website 
at 
www.biologicsinc.com.
If you have questions or need to coordinate shipments in advance, please don’t hesitate 
to contact your Clinical Trial Project Manager at 800/693-4906. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Danika Lew, M.A. 
 
William Barlow, Ph.D. 
Monica Yee 
Joseph Unger, M.S. 
Jo Ann Hartline, M.P.H., M.S.W. 
ED EF
EFFECTIVE 10/01/2015
ISTS
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f Duloxetin
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June 15, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Chairs:    Drs. N.L. Henry 
and A.F. Schott. 
0(025$1'80
Study Chair:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(    ) 
Full board review required. Reason: 
(    ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites of the Holiday closure of Biologics, 
Inc. Biologics, Inc. Clinical Trial Services is FORVHG 7KXUVGD\ -XO\   in
observance of the Independence Day holiday. 
Regular business hours are Monday through Friday, 9:00 a.m. – 6:00 p.m. Eastern. 
For 
additional 
information, 
please 
access 
Biologics’ 
new 
website 
at 
www.biologicsinc.com.
If you have questions or need to coordinate shipments in advance, please don’t hesitate 
to contact your Clinical Trial Project Manager at 800/693-4906. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Danika Lew, M.A. 
 
William Barlow, Ph.D. 
Monica Yee 
Joseph Unger, M.S. 
Jo Ann Hartline, M.P.H., M.S.W. 
D EF
EFFECTIVE 10/01/2015
ISTS
ST
y of Duloxetine
f Duloxetin
keletal Sympt
eletal Sympt
airs:    Drs. N
irs:    Drs. N
h.D.   
D.  
ew required. R
ew required. R
al activation (s
al activation (s
articipate) 
articipate) 
ed risk to pati
ed risk to p
plete study re
lete study re
ddition of tissu
ddition of tiss
Study closure
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Expedited revi
Expedited revi
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 ) No revi
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Distribution Date: 
June 1, 2013 
E-mailed Date: 
May 21, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Coordinators:    Drs. N.L. 
Henry and A.F. Schott. 
0(025$1'80
Study Coordinator:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
(    ) 
Full board review required. Reason: 
(    ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
Increased risk to patient
(   ) 
Complete study redesign
(   ) 
Addition of tissue banking requirements 
(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
( ¥ ) No review required 
0(025$1'80
The purpose of this memorandum is to inform sites of the Holiday closure of Biologics, 
Inc.  Biologics, Inc. Clinical Trial Services is FORVHG 0RQGD\ 0D\   in
observance of the Memorial Day holiday. 
Regular business hours are Monday through Friday, 9:00 a.m. – 6:00 p.m. Eastern. 
For 
additional 
information, 
please 
access 
Biologics’ 
new 
website 
at 
www.biologicsinc.com.
If you have questions or need to coordinate shipments in advance, please don’t hesitate 
to contact your Clinical Trial Project Manager at 800/693-4906. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
Danika Lew, M.A. 
 
William Barlow, Ph.D. 
Monica Yee 
Joseph Unger, M.S. 
Jo Ann Hartline, M.P.H., M.S.W. 
D EFFECTIVE 10/01/2015
OGISTS
STS
udy of Duloxe
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Coordinators: 
Coordinators: 
M.D., Ph.D.   
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May 15, 2013 
TO: 
ALL SWOG MEMBERS, CCOP AND AFFILIATE MEDICAL ONCOLOGISTS 
AND PATHOLOGISTS 
FROM: 
Kimberly F. Kaberle, Protocol Coordinator 
RE:
6, “A Randomized Placebo-Controlled Phase III Study of Duloxetine for 
Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer.” Study Coordinators:    Drs. N.L. 
Henry and A.F. Schott. 
67$786127,&(
Study Coordinator:  Norah Lynn Henry, M.D., Ph.D.    
Phone number: 734/936-4991 
E-mail: norahh@med.umich.edu 
,5%5HYLHZ5HTXLUHPHQWV
 
( ¥ ) 
Full board review required. Reason: 
( ¥ ) 
Initial activation (should your institution choose to 
participate) 
(   ) 
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(   ) 
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(   ) 
Study closure due to new risk information 
(    ) Expedited review allowed 
(    ) No review required 
$&7,9$7,21
The study referenced above is now open for participation.  Entire copies of the protocol 
are enclosed for your use. 
This memorandum serves to notify the NCI and SWOG Statistical Center. 
cc: 
PROTOCOL & INFORMATION OFFICE 
 
William Barlow, Ph.D. 
Joseph Unger, M.S. 
 
Danika Lew, M.A. 
 
Monica Yee 
 
Jo Ann Hartline, M.P.H., M.S.W. 
ED EFFECTIVE 10/01/2015
OGISTS
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oskeletal Sym
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Coordinators: 
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This 


Revised 9/18/13
Revised 4/29/14
S1202
Revised 11/22/13
Revised 1/19/15
Page 1 
Revised 1/23/14
Version Date 1/19/15
PRIVILEGED COMMUNICATION
Activated 5/15/13
FOR INVESTIGATIONAL USE ONLY
6:2*
A RANDOMIZED PLACEBO-CONTROLLED PHASE III STUDY OF DULOXETINE FOR TREATMENT 
OF AROMATASE INHIBITOR (AI)-ASSOCIATED MUSCULOSKELETAL SYMPTOMS IN WOMEN WITH 
EARLY STAGE BREAST CANCER
NCT#01598298
678'<&+$,56
$*(176: 
Norah Lynn Henry, M.D., Ph.D. (Medical Oncology
Duloxetine hydrochloride (NSC-744012)
and Translational Medicine)
(IND-exempt)
University of Michigan 
Comprehensive Cancer Center
1500 E. Medical Center Drive, Med Inn Building C450
Ann Arbor, MI 48109
Phone: 734/936-4991
FAX: 734/936-4940
E-mail: norahh@med.umich.edu
%,267$7,67,&,$16
Anne F. Schott, M.D. (Medical Oncology)
Joseph Unger, Ph.D. (Biostatistics)
University of Michigan
Danika Lew, M.A.
Comprehensive Cancer Center
SWOG Statistical Center
1500 E. Medical Center Drive, Med Inn Building C450
Fred Hutchinson Cancer Research Center
Ann Arbor, MI 48109
1100 Fairview Avenue North, M3-C102
Phone: 734/936-4991
PO Box 19024
FAX: 734/936-4940
Seattle, WA 98109-1024
E-mail: aschott@med.umich.edu
Phone: 206/667-4623
FAX: 206/667-4408
E-mail: junger@fhcrc.org 
E-mail: dlew@fhcrc.org 
3$57,&,3$176
$//,$1&(/Alliance for Clinical Trials in Oncology
(&2*$&5,1/ECOG-ACRIN Cancer Research Group
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Page 2 
Version Date 1/19/15
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1.1
Primary Objectives..................................................................................................... 6
1.2
Secondary Objectives ................................................................................................ 6
1.3
Additional Exploratory Objectives .............................................................................. 6
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3.1
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3.2
Placebo Information ...................................................................................................16
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5.1
Disease Related Criteria ............................................................................................19
5.2
Clinical/Laboratory Criteria.........................................................................................19
5.3
Specimen Submission Criteria...................................................................................21
5.4
Regulatory Criteria .....................................................................................................21
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7.1
Treatment...................................................................................................................22
7.2
Study Plan..................................................................................................................22
7.3
Drug Compliance Documentation ..............................................................................24
7.4
Criteria for Discontinuation from Protocol Intervention ..............................................24
7.5
Discontinuation of Treatment .....................................................................................24
7.6
Follow-Up Period........................................................................................................24
7.7
Unblinding ..................................................................................................................24
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NCI Common Terminology Criteria for Adverse Events ............................................25
8.2
General Considerations .............................................................................................25
8.3
Dose Modifications.....................................................................................................25
8.4
Dose Modification Contacts .......................................................................................26
8.5
Adverse Event Reporting ...........................................................................................26
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10.1 
Primary Outcome .......................................................................................................30
10.2
Main Secondary Outcome..........................................................................................30
10.3
Performance Status....................................................................................................30

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11.1
Primary Objective.......................................................................................................30
11.2
Accrual Monitoring .....................................................................................................32
11.3
Secondary Endpoints................................................................................................. 32
11.4
Data and Safety Monitoring Committee.....................................................................33
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13.1
Registration Timing ....................................................................................................34
13.2
Investigator/Site Registration .....................................................................................34
13.3
OPEN Registration Requirements .............................................................................34
13.4
Registration procedures.............................................................................................35
13.5
Exceptions to SWOG registration policies will not be permitted................................36
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14.1
Data Submission Requirement ..................................................................................36
14.2
Master Forms.............................................................................................................36
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 3 
Version Date 1/19/15
Revised 9/18/13
Revised 4/29/14
Revised 1/19/15
14.3
Data Submission Procedures ....................................................................................36
14.4
Data Submission Overview and Timepoints ..............................................................37
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15.1
Correlative Studies and Banking................................................................................39
15.2
Patient Questionnaires: Instructions for Administration.............................................40
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16.1
Adverse Event Reporting Requirements....................................................................42
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18.1
Determination of Expedited Adverse Event Reporting Requirements.......................49
18.2
6 Intake Calendar ..............................................................................................51
18.3
Guidelines for Emergency Unblinding of Coded Drug...............................................52
18.4
IND Exemption Letter................................................................................................. 54
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 4 
Version Date 1/19/15
Appended 9/18/13
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CTSU Regulatory Office
1818 Market Street,
Suite 1100
Philadelphia, PA19103
Fax: 215-569-0206
Email: 
CTSURegulatory@ctsu.coccg.org
For more information, call the 
CTSU Help Desk at 888-823-5923 
or the Regulatory Help Desk at 
866-651-CTSU.
Please refer to the
patient enrollment
section for 
instructions on 
using the OPEN
system.
Online Data Submission:  This protocol will 
use Medidata Rave® for electronic data 
submission.  Access Rave® using your active 
CTEP-IAM userid and password at the
following url:
https://login.imedidata.com/selectlogin
Other Tools and Reports:  Institutions
participating through the CTSU continue to 
have access to other tools and reports 
available on the SWOG Workbench.  Access 
this by using your active CTEP-IAM userid 
and password at the following url:
https://crawb.crab.org/TXWB/ctsulogon.aspx
The VWXG\SURWRFRODQGDOOUHODWHGIRUPVDQGGRFXPHQWVmust be downloaded from the protocol-
specific Web page of the CTSU Member Web site located at https://www.ctsu.org. Sites must use the
current form version and adhere to the instructions and submission schedule outlined in the protocol.
CTSU sites should follow procedures outlined in the protocol for Site registration, Patient Enrollment, 
Adverse Event Reporting, Data Submission (including ancillary studies), and Drug Procurement.
)RUSDWLHQWHOLJLELOLW\TXHVWLRQVcontact the SWOG Data Operations Center by phone or email:
206-652-2267
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S1202
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Women with hormone receptor-positive breast cancer who are receiving AIs and report average pain of at 
least 4 (out of 10) that has started or increased since initiation of AI treatment
Blood for DNA and serum biomarkers prior to beginning protocol treatment* 
Blinded Drug
vs
Blinded Drug
(Duloxetine or Placebo)
(Duloxetine or Placebo)
Daily x 91 days (13 weeks) 
Daily x 91 days (13 weeks)
Days 15 and 43 (at 2 and 6 weeks): 
Staff administered assessments, patient-completed questionnaires
Day 85 (at 12 weeks): 
Staff administered assessments, patient-completed questionnaires
Blood for serum biomarkers*
Day 99 (at 14 weeks): 
Staff administered telephone assessment of adverse events following 
discontinuation of protocol treatment.
Day 169 (at 24 weeks): 
Staff administered assessment, patient completed questionnaire
* See Section 15.1 for specimen submission instructions.
RANDOMIZE
CLOSED EFFECTIVE 10/01/2015
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S1202
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
2%-(&7,9(6
1.1
Primary Objectives
a.
To assess whether daily duloxetine decreases average joint pain in women with
aromatase 
inhibitor-associated 
musculoskeletal 
syndrome 
(AIMSS), 
as 
measured at 12 weeks by the modified Brief Pain Inventory Short Form (BPI-
SF). 
1.2
Secondary Objectives 
b. 
To assess whether daily duloxetine decreases worst joint pain in women with 
AIMSS, as measured at 12 weeks by the modified BPI-SF. 
c. 
To assess whether daily duloxetine decreases pain interference in women with 
AIMSS, as measured at 12 weeks by the modified BPI-SF. 
1.3
Additional Exploratory Objectives
d.
To investigate whether daily duloxetine improves functioning, pain, and stiffness 
in the knees/hips according to the Western Ontario and McMaster Universities 
Osteoarthritis (WOMAC) scale;  
e.
To investigate whether daily duloxetine improves function, pain and stiffness in 
the hands according to the Modified Score for the Assessment and Quantification 
of Chronic Rheumatoid Affections of the Hands (M-SACRAH);
f.
To investigate whether daily duloxetine improves functional quality of life as 
measured by the Functional Assessment of Cancer Therapy-Endocrine Scale 
(FACT-ES);  
g.
To investigate whether daily duloxetine improves the proportion of patients 
reporting changes for the better versus worst as measured by the Global Rating 
of Change Scale;
h.
To investigate whether daily duloxetine improves/decreases analgesic use;
i.
To investigate whether daily duloxetine improves/increases adherence to, and 
reduces the discontinuation rate for, aromatase inhibitor (AI) therapy.
j.
To assess whether patients receiving duloxetine as compared to placebo have 
improved depression as measured by the Patient Health Questionnaire (PHQ-9)
at Weeks 6 and 12 (for patients experiencing depression at baseline).
k.
To explore the relationship between inherited variants in genes responsible for 
duloxetine metabolism and activity (COMT, HTR3A, SLC6A2, SLC6A4, CYP1A2, 
CYP2D6) and aromatase (CYP19A1) and change in pain with 12 weeks of 
treatment.
l.
To explore the impact of treatment on serum inflammatory cytokine levels with 12 
weeks of treatment at baseline and 12 weeks.
m.
To bank blood samples for future correlative analyses.


CLOSED EFFECTIVE 10/01/2015
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S1202
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
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
Almost 180,000 women are diagnosed with breast cancer each year in the United States. (1) The 
incidence of breast cancer increases with age; approximately 75% of patients are 
postmenopausal at the time of diagnosis. In addition, hormone receptors (HR) are over 
expressed on 80% of breast cancer tumors in postmenopausal women. Therefore, more than 
100,000 postmenopausal women who are diagnosed with breast cancer each year in this country 
are potential candidates for anti-endocrine breast cancer therapy.
Two classes of anti-endocrine therapies are used for treatment of HR-positive breast cancer: 
tamoxifen and the aromatase inhibitors (AIs). AIs can only be used to treat postmenopausal 
women because they are ineffective in women with functional ovaries. Because of their superior 
efficacy, AIs are increasingly used for adjuvant treatment of postmenopausal women with HR-
positive breast cancer. Based on currently available data, women are treated with either 
tamoxifen or AI therapy for 5 years, although studies are underway to determine if treatment
should be continued for a longer period of time.
$,DVVRFLDWHG0XVFXORVNHOHWDO6\PSWRPV$,066
Initial studies suggested that AIs are fairly well tolerated medications. However, it has been 
increasingly recognized that arthralgias are a significant AI-associated toxicity, affecting as many 
as 50% of patients. (2,3) No factors associated with breast cancer treatment (such as 
chemotherapy) or co-morbid conditions (such as diabetes or body mass index) have been clearly 
shown to be predictive of the development of arthralgias. (3) The etiology of AI-associated 
musculoskeletal symptoms remains elusive.  The hypotheses include direct effects of estrogen 
deprivation on bone, neurohormonal changes which result in change of pain sensitivity, and 
immune system changes resulting in alteration of circulating or local inflammatory cytokine 
concentrations. 
A greater than 20% treatment discontinuation rate due to AI-associated arthralgias in a 
prospective trial of AI therapy was reported. (4,5) Based on the number of patients treated with 
aromatase inhibitor therapy and the incidence of musculoskeletal symptoms that occur with 
therapy, as many as 40,000 women are affected by this toxicity in the United States annually. 
More importantly, up to 20,000 women discontinue these potentially life-saving medications 
because of intolerable arthralgias and myalgias. 
No effective pharmacologic therapy has yet been identified for management of these symptoms, 
as many patients do not experience relief of symptoms with analgesic therapy. The current 
treatment for AIMSS is limited to oral analgesics and exercise.  Neither has optimal effect, and
long term use of oral analgesics is problematic.  Six weeks of acupuncture therapy has been 
shown to be beneficial compared to sham acupuncture, but long-term benefit of this treatment is 
unclear. (6)  
Investigators at the University of Michigan recently conducted a Phase II open-label clinical trial of 
duloxetine in 35 postmenopausal women who had been treated with AI therapy for at least 2 
weeks and who developed new or worsening pain after starting AI therapy (details below). This
definitive multi-institutional randomized, placebo-controlled Phase III trial is founded upon the 
positive results of the pilot study. 
'XOR[HWLQH
Duloxetine is a selective serotonin- and norepinephrine-reuptake inhibitor (SNRI) which is FDA-
approved for the treatment of major depressive disorder (MDD), diabetic peripheral neuropathic 
pain, generalized anxiety disorder, fibromyalgia, and chronic musculoskeletal pain, including 
osteoarthritis (OA) and low back pain. (7-14) Small uncontrolled studies have also demonstrated 
that it is potentially effective for treatment of menopausal symptoms and sleep disturbances. 
(17,18)  
CLOSED EFFECTIVE 10/01/2015
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Multiple duloxetine doses and schedules have been studied in these various clinical scenarios. 
(10,11,13,22) In general, duloxetine 60 mg daily was effective and relatively well tolerated in the 
majority of trials. Some studies demonstrated improved tolerability with a dose-escalation rather 
than initiation of treatment at the effective dose. Improvement in pain control occurred rapidly in 
all studies, which typically demonstrated a partial response within 1 to 2 weeks and near maximal 
response within 6 weeks. In studies of patients with fibromyalgyia, the improvement in BPI 
average pain score was independent of the presence of major depressive disorder. 
A small study demonstrated a possible effect of duloxetine therapy on menopause-related 
symptoms in women with depression. (18) In the 14 postmenopausal patients with MDD who 
completed the study, improvement was noted in vasomotor, sleep, and anxiety symptoms. 
Overall pain and pain interference also improved significantly compared to baseline.
The mechanism of action of duloxetine is not completely understood. Descending noxious 
inhibitory control (DNIC) is one of several endogenous central nervous system mechanisms 
involved in the modulation of pain. Attenuated DNIC is believed to reflect altered descending 
inhibitory pain pathways, and has been consistently observed to be attenuated or absent in 
approximately two-thirds of patients with chronic pain disorders such as fibromyalgia, compared 
to approximately 20% of healthy controls. (23-26) In addition, attenuated DNIC is associated with 
decreased red nucleus activation on functional neuroimaging in fibromyalgia patients as 
compared to healthy controls. This decreased DNIC activity can lead to increased sensitivity to 
pain, which is believed to be mediated in part by an attenuated serotonin-norepinephrine system. 
(27) Therefore, treatment with duloxetine, which inhibits serotonin and norepinephrine reuptake, 
may augment and restore DNIC in patients with chronic pain, resulting in decreased pain.
'XOR[HWLQHIRU$,066  
A Phase II open-label clinical trial of duloxetine in 35 postmenopausal women who had been 
treated with AI therapy for at least 2 weeks and who developed new or worsening average pain 
after starting AI therapy that was rated at least 4 on a 10 point Visual Analog Scale was recently 
conducted at the University of Michigan. (16) Subjects were treated with duloxetine 30 mg daily 
for one week, and then 60 mg daily for 7 weeks, with the option of increasing the dose to 60 mg 
twice daily after 3 weeks depending on patient-perceived response to therapy. Benefit from 
therapy was defined as a 30% decrease in average pain score from baseline to 8 weeks as 
assessed using the Brief Pain Inventory (BPI).
Figure 1. Average pain over time during duloxetine therapy in AI-treated patients. Number of 
evaluable patients at each timepoint is listed below the graph.
CLOSED EFFECTIVE 10/01/2015
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S1202
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Of the 29 evaluable patients who initiated protocol-directed therapy, 21 (72.4%) experienced the 
protocol-specified primary endpoint of at least a 30% decrease in average pain score with 8 
weeks of therapy, and 16 (55.2%) experienced at least a 50% decrease in average pain score. 
The mean percent reduction in average pain from baseline to 8 weeks was 60.9% with a 95% CI 
of 48.6%-73.1% (Figure 1, Table 1). Nineteen (65.5%) experienced at least a 30% decrease in 
worst pain with 8 weeks of therapy, and 17 (58.6%) experienced at least a 50% decrease in worst 
pain. The mean percent reduction in worst pain from baseline to 8 weeks was 59.9% (95% CI 
47.0%-72.7%). Change in interference of pain with activities of daily living as measured using the 
BPI demonstrated that the mean percent reduction in pain interference with 8 weeks of duloxetine 
therapy was 78.9% (95% CI 68.1-89.8%). Only 1 subject chose to increase the dose of duloxetine 
to 60 mg twice daily after 4 weeks of therapy. Eighteen of the 23 patients (78.3%) who completed 
all 8 weeks of study treatment chose to remain on duloxetine therapy. After completion of study 
therapy, 3 patients discontinued treatment because of lack of improvement in pain symptoms, 
and 2 chose to stop therapy because of duloxetine-associated side effects. 
Multiple patient-completed questionnaires were utilized to capture information related to changes 
in pain symptoms (Brief Pain Inventory [BPI] and pain visual analog scale [VAS]), functional 
status (Health Assessment Questionnaire), depressive symptoms (CES-D), vasomotor symptoms 
(Hot Flash Related Daily Interference Scale (HFRDIS), Menopause-Specific Quality of Life-
Intervention Questionnaire (MENQOL-I)), and sleep quality (Pittsburgh Sleep Quality Index), 
during the 8 week study period. (28-32) Results suggest that duloxetine therapy leads to 
improvements in functional status and depression, and may lead to small improvements in hot 
flashes and sleep.
Safety was assessed in all 34 patients who received at least one dose of study medication. 
Adverse events and treatment discontinuation rates were similar to previously reported duloxetine 
studies (10,11,19,20) Seven patients (20.6%) discontinued therapy due to adverse events. The 
majority of subjects who discontinued therapy because of adverse events did so within a few 
days of starting treatment. Reasons for treatment discontinuation included Grade 1 and/or 2 
drowsiness, headache, and nausea. The majority of reported adverse events were Grade 1
and/or 2 fatigue and drowsiness, nausea, xerostomia, constipation, and headache, consistent 
with prior studies of duloxetine, and 76.5% of patients reported at least one adverse event. The 
only Grade 3 or 4 adverse event reported was tachycardia, thought by the treating physician to be 
unlikely related to treatment. Since AI therapy acts by suppressing estradiol production, the 
impact of duloxetine therapy on serum estradiol concentration was assessed. Duloxetine therapy 
did not affect serum estradiol concentrations in the 23 subjects who completed 8 weeks of 
treatment.
CLOSED EFFECTIVE 10/01/2015
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Table 1. Change in outcome measures with duloxetine therapy (n=29). 
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Average pain (0-10)
5.5 (1.1)1
2.5 (1.5)
2.1 (2.0)
2.3 (1.8)
2.1 (1.6)
<0.0001
Worst pain (0-10)
7.2 (1.4)
3.4 (2.4)
3.1 (2.6)
3.3 (2.0)
2.9 (2.3)
<0.0001
Pain interference 
(0-10)
4.3 (2.0)
1.6 (1.7)
1.3 (1.7)
1.1 (1.0)
1.0 (1.3)
<0.0001
HAQ (0-3)
0.48 
(0.31)
0.20 
(0.26)
0.25 
(0.33)
0.21 
(0.29)
0.23 
(0.28)
0.001
Hot flash interference 
(0-100; HFRDIS)
17.1 
(21.9)
10.1 
(14.5)
7.0 (12.5)
0.02
Hot flash interference 
(1-8; MENQOL 
vasomotor subscale)
2.9 (2.0)
2.2 (1.4)
2.6 (1.7)
0.31
Depression (CESD)
10.1 (8.8)
5.8 (4.7)
3.5 (3.2)
0.004 
Sleep (0-21)
8.0 (3.3)
7.8 (4.1)
6.9 (4.0)
0.03
1 Baseline to 8 weeks columns show mean score (SD)
2 Comparison between baseline and 8 weeks 
&RUUHODWLYHVWXGLHV  
Identification of patients who are more likely to respond to duloxetine therapy prior to treatment 
initiation could impact management of AIMSS and could yield additional information regarding the 
mechanism underlying development of AIMSS. Potential approaches for identifying predictive 
markers of response to therapy include evaluation of associations with inherited genetic variants 
in candidate genes and with baseline or change in circulating inflammatory markers.
Inherited genetic variants in genes associated with duloxetine metabolism or activity could 
potentially influence response to or toxicity from therapy. Alternatively, patients who harbor a 
specific genetic variant and subsequently develop AIMSS may be more likely to respond to 
duloxetine. For example, a genetic variant in the COMT gene has been associated with chronic 
pain, including osteoarthritis and temporomandibular joint disorder. (33) In a study of patients with 
radiographically-documented arthritis, patients with the high pain sensitivity haplotype of the 
COMT gene were more likely to develop pain compared to those without that haplotype. (34)
Recently, a single nucleotide polymorphism (SNP) in COMT was found to be associated with 
increased post-surgical pain and fatigue in breast cancer survivors. (35,36) In addition, a different 
SNP in COMT has also been associated with response to duloxetine and to the related SNRI 
milnacipran in MDD. (37,38) SNPs in serotonin and norepinephrine transporters have been 
associated with duloxetine-associated toxicities.(Lilly Pharmaceuticals, unpublished observation) 
In addition, it has previously been demonstrated that inherited genetic variants in multiple genes,
including aromatase and the inflammatory cytokine interleukin-6 (IL-6), may predispose patients 
to development of AIMSS. (39,40) Finally, in a prospective clinical trial of AI therapy we 
demonstrated potential associations between SNPs in estrogen receptor alpha and aromatase 
and the estrogen receptor and discontinuation of AI therapy due to toxicity. (Henry et al,
submitted) Therefore, there are a number of genetic variants in candidate genes that may be 
associated with response to duloxetine therapy in women with AIMSS. 
CLOSED EFFECTIVE 10/01/2015
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Treatment-associated changes in serum concentrations of inflammatory cytokines have been 
demonstrated in patients with chronic pain. In addition, a recent study of patients with major 
depression treated with duloxetine found that serum IL-6 concentrations increased in those 
patients who responded to therapy. (41) Although there are minimal data to suggest that women 
with AIMSS have altered levels of circulating inflammatory markers prior to therapy, it is possible 
that treatment with a medication such as duloxetine could impact serum concentrations of pro- or 
anti-inflammatory factors, or that subsets of women who have altered levels prior to treatment 
initiation could be more likely to benefit. Given the paucity of data, however, these investigations 
would be purely exploratory.
6XPPDU\This is a Phase III randomized, placebo-controlled clinical trial of duloxetine 60 mg 
daily versus placebo that aims to evaluate the benefit of duloxetine for management of AIMSS
and other related symptoms that can impact quality of life, such as depression, anxiety, hot 
flashes, and sleep quality. We will perform exploratory correlative studies for hypothesis
generation. Improvement in treatment-related symptoms may improve persistence with AI 
therapy, and thereby lead to improved breast cancer outcomes.

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This study was designed to include women and minorities, but was not designed to measure 
differences of intervention effects.  The anticipated accrual in the ethnicity/race and sex 
categories is shown in the table below. Aromatase inhibitors are not used in men with breast 
cancer, so men will not be included in this study.
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Duloxetine hydrochloride (Cymbalta®) (NSC-744012)
a. 
PHARMACOLOGY
Mechanism of Action: Duloxetine, a SNRI, is a potent inhibitor of neuronal 
serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine 
reuptake. 
CLOSED EFFECTIVE 10/01/2015
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S1202
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b. 
PHARMACOKINETICS
1.
Absorption: Orally administered duloxetine is well absorbed. There is a 
median 2 hour lag until absorption begins (Tlag), with maximal plasma
concentrations (Cmax) of duloxetine occurring 6 hours post dose. Food 
does not affect the Cmax of duloxetine, but delays the time to reach peak 
concentration from 6 to 10 hours and it marginally decreases the extent 
of absorption (AUC) by about 10%. There is a 3 hour delay in absorption 
and a one-third increase in apparent clearance of duloxetine after an 
evening dose as compared to a morning dose.
2.
Distribution: The apparent volume of distribution averages about 1640 L. 
Duloxetine is highly bound (>90%) to proteins in human plasma, binding 
SULPDULO\ WR DOEXPLQ DQG Į1-acid glycoprotein. The interaction between 
duloxetine and other highly protein bound drugs has not been fully 
evaluated. Plasma protein binding of duloxetine is not affected by renal 
or hepatic impairment.
3.
Metabolism: Duloxetine undergoes extensive metabolism to numerous 
metabolites, however the major circulating metabolites have not been 
shown to contribute significantly to the pharmacologic activity. The major 
biotransformation pathways for duloxetine involve oxidation of the 
naphthyl ring by CYP1A2 and CYP2D6 followed by conjugation and 
further oxidation. Metabolites found in plasma include 4-hydroxy 
duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. 
Many additional metabolites have been identified in urine, some 
representing only minor pathways of elimination. Only trace (<1% of the 
dose) amounts of unchanged duloxetine are present in the urine. Most 
(about 70%) of the duloxetine dose appears in the urine as metabolites
of duloxetine; about 20% is excreted in the feces. 
4.
Elimination: Duloxetine has an elimination half-life of about 12 hours 
(range 8 to 17 hours) and its pharmacokinetics are dose proportional 
over the therapeutic range. Steady-state plasma concentrations are 
typically achieved after 3 days of dosing. 
c. 
ADVERSE EFFECTS
1.
Refer to the package insert or manufacturer website for the most 
complete and up to date information on contraindications, warnings and 
precautions, and adverse reactions.
$GYHUVH5HDFWLRQV
!

Cardiovascular
Palpitation
Central nervous 
system
Headache
Somnolence
Fatigue
Insomnia
Agitation
Anxiety
Abnormal dreams
Yawning
Hypoesthesia
Lethargy
Vertigo 
Chills
CLOSED EFFECTIVE 10/01/2015
od
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 for duloxet
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ADVERSE E
DVERSE E
1.
1.


S1202
Page 13
Version Date 1/19/15
Dermatologic
Hyperhydrosis
Endocrine & 
metabolic
Decreased libido
Hot flashes
Sexual dysfunction
Gastrointestinal
Nausea
Xerostomia
Constipation
Diarrhea
Decreased appetite
Abdominal pain
Vomiting
Dyspepsia
Weight loss
Flatulence
Abnormal taste
Weight gain
Genitourinary
Erectile dysfunction
Delayed ejaculation
Ejaculatory dysfunction
Hepatic
ALT  > 3x ULN
Neuromuscular & 
skeletal
Muscle spasms
Tremor
Musculoskeletal pain
Paresthesia
Rigors
Ocular
Blurred vision
Respiratory
Nasopharyngitis
Cough
Miscellaneous
Influenza
The following serious or life-threatening adverse reactions occurred in 
less than 1% of patients: Alkaline phosphatase increased, anaphylactic 
reaction, angioneurotic edema, apathy, bruxism, contact dermatitis, 
dehydration, dermatitis, diastolic blood pressure increased, diplopia, 
disorientation, dysarthria, dyskinesia, dysuria, eructation, erythema, 
erythema 
multiforme, 
EPS, 
gastritis, 
gastroenteritis, 
glaucoma, 
gynecological bleeding, hallucinations, Hb A1c increased, hepatic failure, 
hepatitis, 
hepatomegaly, 
hyperbilirubinemia, 
hypercholesterolemia, 
hyperglycemia, hyperlipidemia, hypersensitivity, hypertensive crisis, 
hyponatremia, hypothyroidism, jaundice, malaise, mania, MI, micturition 
urgency, mood swings, muscle spasm, muscle tightness, muscle 
twitching, night sweats, nocturia, orthostatic hypotension, peripheral 
coldness, photosensitivity, polyuria, rash, restless leg syndrome, seizure, 
serotonin syndrome, SIADH, Stevens-Johnson syndrome, stomatitis, 
supraventricular arrhythmia, syncope, systolic blood pressure increased, 
tachycardia, thirst, throat tightness, transaminases increased, trismus, 
urinary retention, urticaria
2.
Contraindications: Uncontrolled narrow-angle glaucoma.
Estimated 
creatinine clearance < 30 ml/min.
3.
Pregnancy and Lactation: Pregnancy Category C. Duloxetine is excreted 
into the milk of lactating women. Nursing while on duloxetine is not 
recommended.
CLOSED EFFECTIVE 10/01/2015
taste
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t gain
015
ctile dysfunctio
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Delayed ejacula
layed ejac
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Revised 9/18/13
S1202
Revised 11/22/13
Page 14
Revised 1/23/14
Version Date 1/19/15
4.
Drug Interactions: Duloxetine is metabolized by both CYP1A2 and 
CYP2D6. Refer to the Cytochrome P450 Drug Interaction Tables 
provided by the Pharmaceutical Management Branch (PMB) available at 
http://ctep.cancer.gov/branches/pmb/. All drugs co-administered with 
duloxetine should be evaluated for potential drug interactions. Questions 
should be addressed to the SWOG Study Chair. 
CYP1A2 Inhibitors 
Do not co-administer with duloxetine.
CYP2D6 Inhibitors
Results in higher concentrations of 
duloxetine (on average of 60%).
Drugs Metabolized by 
CYP2D6
Co-administration of duloxetine with drugs 
that are extensively metabolized by 
CYP2D6 and that have a narrow
therapeutic index should be approached 
with caution.
Warfarin
Carefully monitor when duloxetine is 
initiated or discontinued due to potential 
effect of serotonin on platelets.
Monoamine Oxidase 
Inhibitors (MAOIs)
Co-administration with duloxetine is 
CONTRAINDICATED. MAOI therapy 
must be stopped for 14 days before 
duloxetine is initiated. Treatment with 
MAOIs should not be initiated until 5 days 
after the discontinuation of duloxetine.
d. 
DOSING & ADMINISTRATION
1.
Dosing – See Treatment Plan in Section 7.1. 
2.
Administration:  Duloxetine should be swallowed whole and should not 
be chewed or crushed, nor should the capsule be opened and its 
contents sprinkled on food or mixed with liquids. Duloxetine can be given 
without regard to meals.
3.
Duloxetine should be administered with caution in patients with renal and 
hepatic impairment.
e. 
STORAGE & STABILITY
Store at room temperature (15°C to 25°C). Do not refrigerate or freeze.
f. 
HOW SUPPLIED 
1.
Duloxetine or placebo is available as delayed released 30 mg capsules 
packaged in bottles of 7 or 154 capsules for this study. 
2.
Duloxetine or placebo is supplied free of charge by Lilly for distribution by 
Biologics, Inc.
3.
6:2*,QVWLWXWLRQV: Upon randomization to the study, SWOG will notify 
Biologics, Inc. via secure data transmission, including randomization 
information. 
1RQ6:2* ,QVWLWXWLRQV: Prior to registering its first patient, the 
institution must provide Biologics, Inc. with its pharmacy information via 
e-mail to clinicalresearchservices@biologicsinc.com.
CLOSED EFFECTIVE 10/01/2015
e.
15
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%).
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Revised 1/23/14
S1202
Page 15
Version Date 1/19/15
This communication must include the following information:
x
Name of institution;
x
NCI CODE of institution
x
Head CRA name, telephone number and e-mail address;
x
Names of all investigators at that institution who are participating 
in the protocol;
x
Name, telephone number and e-mail address of pharmacy 
contact person;
x
Shipping address (street, city, state, zip code/postal code) for 
phamacy
These institutions must notify Biologics, Inc. promptly if there is any 
change in the above information.  Once the information is on file at 
Biologics, Inc., requests for initial supplies of study drug will be 
automatically generated based on the participant’s registration date.
$OO ,QVWLWXWLRQV: Orders received before 2 p.m. EST Monday through 
Friday will be processed and shipped for next business day delivery. 
Orders received after 2 p.m. Monday through Friday will be processed 
and shipped the next business morning. All shipments will be sent via 
FedEx for Priority Overnight delivery. Biologics will be closed the 
following holidays: New Years Eve, New Years Day, Memorial Day, 
Independence Day, Labor Day, Thanksgiving, Thanksgiving Friday, 
Christmas Eve, and Christmas Day.
Upon receipt of patient registration and randomization notification, 
Biologics will:
x
Place a call to the study site confirming the order was received, while 
providing the estimated day and time of arrival for the study drug. 
x
Prepare shipment of patient-specific drug. Shipments will include 3 
bottles (Bottles 1 & 3 will have 7 tablets of 30 mg duloxetine or 
placebo; Bottle 2 will have 154 tablets of 30 mg duloxetine or 
placebo) of study drug to cover the 12 week treatment period 
accompanied by a patient-specific labeled resealable bag.
x
Process and ship authorized and completed orders “same day” of 
order receipt if received before 2:00 p.m. E.T. Monday through 
Friday. Authorized and completed orders received after 2:00 p.m. 
E.T. Monday through Friday will be processed and shipped the next 
business day.
x
Each shipment includes a patient label on the resealable bags with 
the following information:
o
Study Number
o
IND caution statement and/or local regulatory statements
o
Drug identification 
o 
Expiration date
o
Storage conditions
o
Detailed dosing instructions
o
Subject ID number, initials, and date dispensed
Packages are tracked until confirmed delivered and delivery exceptions 
are managed with the highest level of urgency to ensure therapy start 
date adherence. Packing slips with the shipment tracking number will be 
faxed to the designated site coordinator for all shipments.
CLOSED EFFECTIVE 10/01/2015
g 
g
rmacy 
macy
 code) for 
code) 
ly if there is 
f there is
mation is on 
ation is on
f study drug
f study dru
nt’s registration
nt’s registratio
2 p.m. EST 
2 p.m. EST 
for next bus
r next bu
y through Frid
through Fr
orning. All shi
ng. All sh
delivery.
del
Biol
io
rs Eve, New 
rs Eve,
r Day, Thank
Day, Than
stmas Day.
tmas Day.
atient registr
atient registr
call to the stud
all to the stud
ing the estima
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bottles (Bottl
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Revised 1/23/14
S1202
Revised 1/19/15
Page 16
Version Date 1/19/15
x
Once study drug is received at the clinical trial site: The 
designated site coordinator verifies and matches the information 
on each of the 3 bottles and labeled resealable bag to the
packing slip, signs off on the packing slip, and faxes completed 
form to Biologics to validate shipment has been received and is 
accurate.
x
The site investigators are responsible to fill in the “Date 
Dispensed” on the label of the resealable bag and each of the 
study drug bottles prior to dispensing the study drugs to the 
patient.
x
The site investigator should provide instructions to subjects on 
drug administration, missed dose, adherence, and drug return.
4.
Drug Accountability
The investigator, or a responsible party designated by the investigator, 
must maintain a careful record of the receipt, disposition, and return of all 
drugs received using the Investigational Agent Accountability Record for 
Oral Agents (Oral DARF). The Oral DARF can be found on the NCI 
home 
page 
(http://ctep.cancer.gov). 
A 
separate 
Blinded 
Drug 
Accountability Record must be maintained for each patient ID number on 
this protocol. Electronic logs are allowed as long as a print version of the 
log process is the exact same appearance as the Oral DARF.
5.
Drug Return and/or Disposition Instruction
a.
Drug Returns: All unused drug (unopened and unused vials 
remaining when a subject goes off treatment, and expired vials) 
should be destroyed on-site in accordance with institutional 
policy and documented accordingly on the DARF. Opened 
bottles with remaining tablets should be documented in the 
patient-specific accountability record (i.e., logged in as "# of 
capsules returned") and destroyed on-site in accordance with 
institutional policy.
b.
Drug Expiration: If packaging does not have expiration date, 
check with drug ordering designee and/or PI at site to confirm 
receipt of ongoing stability testing letter from Lilly when internal 
drug audits are performed. 
6.
Questions about drug orders, transfers, returns or accountability should 
be addressed to
Elliott Lee at Biologics, Inc. (800/693-4906 or 
elee@biologicsinc.com).
3.2
Placebo Information 
a. 
Placebo pellets (Nu-Pareli sugar spheres) filled into size 1 blue/blue capsugel 
shells
b. 
Stability: Expiration after 60 months.
c. 
Storage: Store at room temperature (15°C to 25°C). Do not refrigerate or freeze.

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Breast Cancer Staging Criteria, AJCC 7th Edition, 2009
CLOSED EFFECTIVE 10/01/2015
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policy and 
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S1202
Page 17
Version Date 1/19/15
'(),1,7,212)710
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Definitions for classifying the primary tumor (T) are the same for clinical and for pathologic 
classification. If the measurement is made by physical examination, the examiner will use the 
major headings (T1, T2 or T3). If other measurements, such as mammographic or pathologic 
measurements are used, the subsets of T1 can be used. Tumors should be measured to the 
nearest 0.1 cm increment.
TX  
 
Primary tumor cannot be assessed
T0  
 
No evidence of primary tumor
Tis  
 
Carcinoma in situ
Tis (DCIS) 
Ductal carcinoma in situ
Tis (LCIS) 
Lobular carcinoma in situ
Tis (Paget's) 
Paget's disease of the nipple not associated with invasive carcinoma and/or 
carcinoma in situ (DCIS and/or LCIS0 in the underlying breast parenchyma. 
Carcinomas in the breast parenchyma associated with Paget’s disease are 
categorized based on the size and characteristics of the parenchymal disease, 
although the presence of Paget’s disease should still be noted.
T1 
 
Tumor 20 mm or less in greatest dimension
T1mic   
Microinvasion 1 mm or less in greatest dimension
T1a  
 
Tumor more than 1 mm but no more than 5 mm in greatest dimension
T1b  
 
Tumor more than 5 mm but not more than 10 mm in greatest dimension
T1c  
 
Tumor more than 10 mm but not more than 20 mm in greatest dimension
T2 
Tumor more than 20 mm but not more than 50 mm in greatest dimension
T3
Tumor more than 50 mm in greatest dimension
T4 
Tumor of any size with direct extension to chest wall and/or skin (ulceration or 
skin nodules)
T4a 
Extension to chest wall, not including pectoralis muscle adherence/invasion
T4b 
Ulceration and/or ipsilateral satellite nodules and/or edema (including peau 
d’orange) of the skin, which do not meet the criteria for inflammatory carcinoma
T4c 
Both T4a and T4b
T4d
Inflammatory carcinoma

5HJLRQDO/\PSK1RGHV1
Clinical
NX 
Regional lymph nodes cannot be assessed (e.g., previously removed)
N0 
No regional lymph node metastasis
N1 
Metastasis to movable ipsilateral level I, II axillary lymph node(s)
N2 
Metastasis in ipsilateral level I, II axillary lymph nodes fixed or matted, or in 
clinically detected* ipsilateral internal mammary nodes in the absence of clinically 
evident axillary lymph node metastasis
N2a 
Metastasis in ipsilateral level I, II axillary lymph nodes fixed to one another 
(matted) or to other structures
N2b 
Metastasis only in clinically detected* ipsilateral internal mammary nodes and in 
the absence of clinically evident level I, II axillary lymph node metastasis
N3 
Metastasis in ipsilateral infraclavicular (level III axillary) lymph node(s) with or 
without level I, II axillary lymph node involvement, or in clinically detected* 
ipsilateral internal mammary lymph node(s) and in the presence of clinically 
evident level I, II axillary lymph node metastasis; or metastasis in ipsilateral 
supraclavicular lymph node(s) with or without axillary or internal mammary lymph 
node involvement
CLOSED EFFECTIVE 10/01/2015
he 
e 
ologic 
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 to the
the
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stics of the p
tics of the p
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on
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dimension
dimens
than 5 mm in 
than 5 mm 
ore than 10 mm
than 10 m
t more than 20
t more than 2
not more than
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direct extens
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wall, not includ
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S1202
Page 18
Version Date 1/19/15
N3a 
Metastasis in ipsilateral infraclavicular lymph node(s)
N3b 
Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph 
node(s)
N3c 
Metastasis in ipsilateral supraclavicular lymph node(s)
*Clinically detected is defined as detected by imaging studies (excluding lymphoscintigraphy) or 
by clinical examination and having characteristics highly suspicious for malignancy or a presumed 
pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination.
'LVWDQW0HWDVWDVLV0
M0  
 
No clinical or radiographic evidence of distant metastasis

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Stage IA 
T1*  
 
N0  
 
M0
T0  
 
N1mi   
M0
Stage IB 
T1*  
 
N1mi   
M0
Stage IIA 
T0  
 
N1**  
 
M0
T1*  
 
N1**  
 
M0
T2  
 
N0  
 
M0
Stage IIB 
T2  
 
N1  
 
M0
T3  
 
N0  
 
M0
Stage IIIA 
T0  
 
N2  
 
M0
T1*  
 
N2  
 
M0
T2  
 
N2  
 
M0
T3  
 
N1  
 
M0
T3  
 
N2  
 
M0
Stage IIIB 
T4  
 
N0  
 
M0 
T4  
 
N1  
 
M0
T4  
 
N2  
 
M0
Stage IIIC 
Any T   
N3  
 
M0
* T1 includes T1mic
** T0 and T1 tumors with nodal micrometastases only are excluded from Stage IIA and are 
classified Stage IB
NOTE: Stage designation may be changed if post-surgical imaging studies reveal the presence of
distant metastases, provided the studies are carried out within 4 months of diagnosis in the
absence of disease progression and provided that the patient has not received neoadjuvant
therapy.
CLOSED EFFECTIVE 10/01/2015
or r 
umed
me
tion.
n.
M0
M0
M0
M0
M0
M
M0
M
M
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N1 
N2 
N2
N0 
N
N1 
N
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ny T
es T1mic
es T1m
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nd T1 tum
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fied Stage IB
NOTE: Stage d
NOTE: Stage d
distant meta
distant meta
absence 
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Revised 9/18/13
S1202
Revised 11/22/13
Page 19
Revised 1/19/15
Version Date 1/19/15

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
Each of the criteria in the following section must be met in order for a patient to be considered eligible for 
registration.  Use the spaces provided to confirm a patient's eligibility.  For each criterion requiring test 
results and dates, please record this information on the Onstudy Form (and submit to the Data 
Operations Center in Seattle (see Section 14.0).  Any potential eligibility issues should be addressed to 
the Data Operations Center in Seattle at 206/652-2267 prior to registration.
  
In calculating days of tests and measurements, the day a test or measurement is done is considered Day 
0.  Therefore, if a test is done on a Monday, the Monday 4 weeks later would be considered Day 28.  This 
allows for efficient patient scheduling without exceeding the guidelines.  ,I'D\RUIDOOV
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5.1
Disease Related Criteria
a.
Patients must be women with histologically confirmed estrogen receptor (ER) 
and/or progesterone receptor (PgR) positive invasive carcinoma of the breast
(Stage I-III) with no evidence of metastatic disease (M0).  
b.
Patients must have completed mastectomy or breast sparing surgery, and must 
have recovered from all side effects of the surgery. If patients were treated with 
chemotherapy and/or radiation therapy, these treatments must be completed at 
least 28 days prior to study registration. Patients should have recovered from all 
Grade 2 or higher side effects of chemotherapy and/or radiation therapy with the 
exception of alopecia and peripheral neuropathy.  Concurrent bisphosphonate 
and trastuzumab therapies are allowed.
5.2
Clinical/Laboratory Criteria
a. 
Patients must be post-menopausal, as defined by at least one of the following:
1.
 12 months since the last menstrual period OR
2. 
prior bilateral oophorectomy OR
3. 
previous hysterectomy with one or both ovaries left in place (or previous 
hysterectomy in which documentation of bilateral oophorectomy is 
unavailable) AND (XQOHVVyears of age) FSH values consistent with 
the institutional normal values for the post menopausal state OR
4.
have been on LHRH agonist therapy for at least 3 months and estradiol 
levels drawn within 28 days prior to registration are consistent with the 
institutional normal values for post-menopausal state.
b. 
Patients must currently be taking one of the following aromatase inhibitor (AI) 
doses for at least 21 days prior to registration and plans to continue for at least 
an additional 180 days after registration. Patients may have received any number 
of prior AI therapies, but the first AI therapy must have started no more than 36
months prior to registration.
1. 
anastrozole (Arimidex®) 1 mg daily 
2. 
letrozole (Femara®) 2.5 mg daily
3. 
exemestane (Aromasin®) 25 mg daily
CLOSED EFFECTIVE 10/01/2015
o 
o
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28.  Th
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registration.
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Revised 1/23/14
S1202
Revised 4/29/14
Page 20
Revised 1/19/15
Version Date 1/19/15
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c. 
Patients must have aromatase inhibitor (AI) associated musculoskeletal 
symptoms that began or increased after starting AI therapy. New musculoskeletal 
pain must not be due specifically to fracture or traumatic injury.
d. 
Patients must have completed the 6 Brief Pain Inventory-Short Form (BPI-
SF)  within 7 days prior to registration. Patients must have an “average pain” of at 
least 4 on the BPI-SF (item #4).  
e. 
Patients must have Zubrod performance status of 0-2 (see Section 10.3).
f. 
Patients must have no known allergy or hypersensitivity to duloxetine or any of 
the inactive ingredients in the matching placebo.
g. 
Patients must not have any contraindicated concurrent illnesses listed on the
duloxetine package insert including:
x
Current primary psychiatric diagnosis (schizophrenia, psychosis) or suicidal 
ideation, history or bipolar disorder, or seizure disorder
x
History of alcohol or other substance abuse or dependence within 365 days prior 
to registration.
x
Chronic liver disease
x
End stage renal disease
x
Uncontrolled narrow-angle glaucoma
x
Clinically significant coagulation disorder
h. 
Patients must not take MAO-Inhibitors for 14 days before registration or any time 
during study treatment. Concomitant therapy with heparin and warfarin is also not 
permitted at registration or while on protocol treatment. Aspirin is permitted (see 
Section 8.2).
i. 
Patients must have a calculated creatinine clearance > 30 mL/min. The serum 
creatinine value used in the calculation must have been obtained within 28 days 
prior to registration.
Calculated creatinine clearance = (140 – age) x wt (kg) x 0.85
72 x creatinine (mg/dL)
j. 
Patients must have adequate hepatic function as evidenced by all of the following 
within 28 days prior to registration: AST and ALT both within 3 x Upper Limit of 
Normal based on institutional values, and total bilirubin within the upper limit of 
normal based on institutional values.
k. 
Patients must not require selective serotonin reuptake inhibitors (SSRIs) or 
tricyclic antidepressants during study participation. Patients must have been able 
to taper and discontinue treatment with these medications at least 7 days prior to 
registration (28 days for fluoxetine), and must not be experiencing antidepressant 
withdrawal symptoms (e.g., dizziness, nausea, sleep disturbance, or other 
sensory disturbances). 3DWLHQWV PXVW QRW KDYH SUHYLRXVO\ WDNHQ WKH
VHURWRQLQ QRUHSLQHSKULQH UHXSWDNH LQKLELWRUV 615, GXOR[HWLQH RU
PLOQDFLSUDQ Prior venlafaxine is allowed as long as it was not taken for 
treatment of pain (eg, prior treatment for hot flashes is permitted). 
CLOSED EFFECTIVE 10/01/2015
tal 
al 
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ection 10.
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S1202
Page 21
Version Date 1/19/15
Revised 4/29/14
Revised 1/19/15
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(Section 5.2k contd.)
NOTE:  Patients requiring antidepressants for management of depression are not 
appropriate candidates for this placebo-controlled study, but those who are on 
antidepressants for other indications, such as hot flash management, may be
able to tolerate a time off of antidepressant therapy.
l. 
Patients who are receiving treatment with narcotics, tramadol, gabapentin, and/or 
pregabalin must have been taking a stable dose for at least 30 days prior to 
registration.
m. 
Patients must be able to complete study questionnaires in English or Spanish.
n. 
Patients must not have concurrent medical/arthritic disease that could confound 
or interfere with evaluation of pain or efficacy including: inflammatory arthritis 
(rheumatoid arthritis, systemic lupus, spondyloarthropathy, psoriatic arthritis, 
polymyalgia rheumatica) and cancer involving the bone.
Patients with 
osteoarthritis are eligible.
5.3
Specimen Submission Criteria
a. 
Patients must be willing to submit blood samples for correlative studies as 
outlined in Section 15.0. Baseline samples must be obtained prior to beginning 
protocol treatment.
5.4
Regulatory Criteria
a. 
All patients or their legally authorized representative must be informed of the 
investigational nature of this study and must sign and give written informed 
consent in accordance with institutional and federal guidelines.
b. 
As a part of the OPEN registration process (see Section 13.3 for OPEN access 
instructions) the treating institution's identity is provided in order to ensure that 
the current (within 365 days) date of institutional review board approval for this 
study has been entered in the system.


CLOSED EFFECTIVE 10/01/2015
on are not
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S1202
Page 22
Version Date 1/19/15
Revised 1/19/15

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Patient randomization will be dynamically balanced according to the following stratification 
factors: baseline pain score (BPI-SF item #4) (4-6 vs 7-10); and prior taxane use (yes vs. no). 

75($70(173/$1
For treatment or dose modification related questions, please contact Dr. Lynn Henry
(norahh@umich.edu) at 734/936-4991, or Dr. Anne Schott (aschott@umich.edu) at 734/936-
4991. 
7.1
Treatment  
Agent
Dose
Schedule
Blinded drug 
 
1 capsule PO Daily
Days 1-7 
(duloxetine 30 mg or  
  
placebo) 
 
 
Blinded drug 
 
2 capsules PO Daily
Days 8-84
(duloxetine 30 mg or  
  
placebo) 
Blinded drug 
 
1 capsule PO Daily
Days 85-91
(duloxetine 30 mg or  
placebo) 
 
 
 
 
7.2
Study Plan
a.
Initial Visit
Before beginning the intervention, patients will have a general physical exam 
(including recording of weight and height) and a mandatory blood draw for whole 
blood and serum (see Section 15.1). The patient will complete the 6 Brief 
Pain Inventory–Short Form (BPI-SF) prior to registration to confirm eligibility (see 
Section 5.2d). Patients will complete the following questionnaires prior to 
beginning treatment with blinded study drug:
6 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) 
Index (Version 3.1)
6 Modified-Score for the Assessment and Quantification of Chronic 
Rheumatoid Affections of the Hands (M-SACRAH)
6FACT – ES Trial Outcome Index (Version 4) 
6Patient Health Questionnaire-9 (PHQ-9) 
It should take the patient about 20-25 minutes to complete the questionnaires.  
6HH6HFWLRQIRULQVWUXFWLRQVIRUDGPLQLVWUDWLRQRIWKHTXHVWLRQQDLUHV
The nurse or CRA must complete the 6Cover Sheet for Patient-Completed 
Questionnaires.  
Bottle #1 and #2 are dispensed at this visit. Patients will take 1 capsule daily for 
the first 7 days, then increase the dose to 2 capsules daily. The dose that should 
be taken each day should be listed on the patient calendar (see Section 15.2c.1).
CLOSED EFFE
g 
g 
FECTIVE 10/01/2015
Lynn Henry
Lynn Hen
) at 734/936
at 734/93
Schedule
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S1202
Page 23
Version Date 1/19/15
Revised 1/19/15
b.
Follow-up Visits  
Follow-up visits will occur on Day 15, 43, 85, and 169 after start of treatment.
Drug adherence will be ascertained by the nurse or CRA by review of the patient 
completed 6 Intake Calendar on Day 15, 43, and 85, as well as count of 
blinded drug capsules on the Day 43 and 85 visits. After the Day 85 pill count, 
the nurse or CRA must dispense bottle #3 to the patient to complete the Day 85 
to Day 91 taper.  Counts of blinded drug capsules remaining should be recorded 
on the 6 Treatment Form and the patient’s medical record through the Day 
85 visit. Adherence to AI should be recorded on the 6 Treatment Form at 
every visit. Adverse events will be assessed and recorded on the 6 Adverse 
Event Summary Form through the Day 85 visit. Use of pain medications, 
steroids, physical therapy, and acupuncture will be recorded on the 6
Supplemental Agents Reporting Form.
The nurse or CRA will contact the patient by telephone on Day 99 to assess 
adverse events following study drug discontinuation. Adverse events will be 
recorded on the 6 Adverse Event Summary Form
Patients will be instructed to complete the following questionnaires at the Day 15, 
43,
85, and 169
visits. It takes about 20-25
minutes to complete the 
questionnaires. 
6 Brief Pain Inventory Short Form (BPI-SF) 
6 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) 
Index (Version 3.1) 
6 Modified-Score for the Assessment and Quantification of Chronic 
Rheumatoid Affections of the Hands (M-SACRAH) 
6 FACT – ES Trial Outcome Index (Version 4) 
6 Global Ratings of Change in Joint Pain and Stiffness 
Patients will also be instructed to complete the following self-administered 
questionnaire at the Day 43 and 85 visits. It takes about 5-10 minutes to 
complete the assessment.
6 Patient Health Questionnaire-9 (PHQ-9).
The nurse or CRA will also complete the 6 Cover Sheet for Patient-
Completed Questionnaires at each visit to indicate whether or not the patient 
completed the questionnaires, if the patient required assistance and the method 
for completing the questionnaires.  If one or more of the questionnaires was not 
completed, an overall reason must be indicated on the Cover Sheet.  See 
Section 15.2 for detailed instructions for administration of the questionnaires.
Additionally, at the Day 85 visit, blood will be drawn for serum biomarkers (see 
Section 15.1). 
All patients must taper off study drug after the Day 85 visit by decreasing the 
dose to 1 capsule daily for 7 days. After completing the taper of the study drug, if
a patient wishes to take commercially-available duloxetine, she should take at 
least 7 days of duloxetine 30 mg daily prior to increasing the dose to 60 mg daily, 
in order to minimize the chance of developing side effects. She is permitted to 
start this at any time following completion of the taper of the study drug (Day 92).
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 24
Version Date 1/19/15
Revised 9/18/13
7.3
Drug Compliance Documentation
Drug compliance will be recorded by patients in the Intake Calendar (see Appendix 18.2). 
Institutional CRAs will review and ascertain patient adherence with protocol therapy at 
the end of treatment for each visit.  Calendar should be kept in the patient's clinic chart.  
Note that the Intake Calendar is provided only as a tool for tracking patient compliance.  
Sites may utilize institutional pill diaries or other source documentation in place of the 
Intake Calendar at the discretion of the treating physician.
7.4
Criteria for Discontinuation from Protocol Intervention
a.
Evidence of new cancer (except for basal squamous skin cancer or in situ 
cervical cancer) or cancer recurrence at any time.* 
b.
Unacceptable toxicity.* 
c.   
Delay of study drug for any reason > 28 days.
d.
Completion of 13 weeks of treatment.
e.
Discontinuation of AI therapy or change to a different aromatase inhibitor
medication during protocol treatment.* (Note: a delay of 28 days or more will be 
considered discontinuation of AI therapy.)
f. 
The patient may withdraw from the study at any time for any reason.* 
* If a patient is taking 2 capsules of blinded study drug daily and discontinues therapy 
prior to the Day 85 visit, she should decrease the dose to 1 capsule daily for 7 days prior 
to permanently stopping the blinded study drug. If a patient goes off protocol intervention 
for any reason before the Day 85 visit, the 6 Supplemental Agents Reporting Form 
and the patient questionnaires required at each subsequent visit should continue to be 
administered according to the protocol assessment schedule. See Section 14.4i for off 
protocol intervention data submission requirements.
7.5 
Discontinuation of Treatment
All reasons for discontinuation of intervention must be documented in the Off Treatment 
Notice – Prevention Studies. 
7.6
Follow-Up Period
No further follow-up will be required once the patient completes 24 weeks of study 
participation. 
7.7
Unblinding
Patients may be unblinded to their treatment assignment on request at the end of the 
study, after follow-up for all patients is complete.  Institutions will be notified when patient 
unblinding information is available for the study.  For emergency unblinding criteria and 
procedures, see Section 18.3. 
CLOSED EFFECTIVE 10/01/2015
rt.
nce.
ce
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the 
n cancer or i
cancer or i
ange to a d
ange t
t.* (Note: a de
(Note: a 
herapy.)
apy.)
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m the study a
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es of blinded 
should decreas
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onnaires requ
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on of Treatm
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Revised 4/29/14
S1202
Page 25
Version Date 1/19/15
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8.1
NCI Common Terminology Criteria for Adverse Events 
The CTEP Version 4.0 of the NCI Common Terminology Criteria for Adverse Events 
(CTCAE), will be utilized for AE reporting.  The CTEP CTCAE Version 4.0 is identified 
and located at the CTEP website at 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.
All appropriate treatment areas should have access to a copy of the CTEP Version 4.0 of 
the CTCAE.
8.2
General Considerations
Patients who are taking narcotics, tramadol, gabapentin, and/or pregabalin at study 
registration should continue to take a stable dose of medication or should decrease their 
dose during study participation, as tolerated. Dose increases for these medications 
should be discouraged.
Patients who need additional analgesic medication during study participation are 
requested to take acetaminophen. Patients should not undergo therapy with other 
treatment modalities such as physical therapy, acupuncture, systemic steroids, or intra-
articular steroid injections during study participation unless medically necessary. Usage 
of all medications and other therapies for treatment of pain should be documented on the 
6 Supplemental Agents Reporting Form. 
Caution should be taken if patients take aspirin or non-steroidal anti-inflammatory drugs 
during study participation because of the increased risk of bleeding when these 
medications are used in combination with duloxetine.
Caution should be taken if patients take triptan medications, tramadol, linezolid, or other 
serotonergic medications during study participation because of the increased risk of 
serotonin syndrome when these medications are used in combination with duloxetine.
Duloxetine has been associated with an increased risk of suicide. Therefore, at the day 
43 and 85 study visits, the answer to question #9 on the PHQ-9 should be reviewed 
before the patient leaves the clinic. In addition, all patients should be asked about suicidal 
thoughts or actions at the Day 15 study visit and Day 99 telephone call. If a patient 
reports suicidal thoughts or actions, or answers anything other than “Not at all” to 
question #9, the treating physician should be immediately notified.
NOTE:  Concomitant therapy with heparin and warfarin is not permitted while on study 
treatment. 
8.3
Dose Modifications
*UDGHDQG*UDGH7R[LFLW\
If Grade 1 or 2 toxicities occur that are felt to be possibly, probably, or definitely related to 
study drug, monitor as needed until problem has resolved (i.e., Grade 0), stabilized (i.e., 
remains as Grade 1 or Grade 2), or is otherwise explained. If Grade 1 or Grade 2 
symptoms persist, the local SWOG investigator
will assess whether symptom 
management should be initiated, or whether the dose should be reduced from 2 capsules 
per day to 1 capsule per day. If Grade 1 or 2 symptoms persist while taking 1 capsule per 
day, the local SWOG investigator will assess whether symptom management should be 
initiated (if that has not already been done), or whether the patient should be removed 
from protocol treatment. No dose re-escalations are allowed. Follow-up will be conducted 
at the intervals specified in the protocol.
CLOSED EFFECTIVE 10/01/2015
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8.3
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S1202
Page 26
Version Date 1/19/15
Revised 11/22/13
Revised 4/29/14
*UDGHRU*UDGH7R[LFLW\
If a patient develops any Grade 3 toxicity possibly, probably, or definitely related to the 
study drug, the patient should decrease the dose to 1 capsule daily for 7 days (if deemed 
medically safe to do so). If the symptoms resolve to Grade 0-2, the dose should be 
continued at 1 capsule per day. This dose may be maintained if Grade 3 toxicity does not
recur. If at the 1 capsule a day dose the participant is still experiencing problems, she can 
be given a 1 week drug holiday from the blinded study drug. Subsequently, the patient 
may be re-challenged at the 1 capsule per day dose. Follow-up will continue at the 
intervals specified in the protocol. If symptoms do not recur (i.e., if symptoms resolve to 
Grade 0), the dose should be maintained, and no dose re-escalations are allowed. If 
Grade 3 drug-related toxicity does not improve to a Grade 0, 1, or 2 level within 1 week at 
the reduced dose, the patient should be removed from all protocol treatment. If the 
patient develops any Grade 4 toxicity possibly, probably, or definitely related to the study 
drug, the patient should decrease the dose to 1 capsule daily for 7 days (if deemed 
medically safe to do so) and then be removed from protocol treatment. Patient will also 
be removed from protocol treatment if there is a delay of study intervention >28 days.
8.4
Dose Modification Contacts 
For treatment or dose modification questions, please contact Dr. Lynn Henry at 734/936-
4991 (norahh@umich.edu), or Dr. Anne Schott at 734/936-4991 (aschott@umich.edu). 
8.5
Adverse Event Reporting
Toxicities (including suspected reactions) that meet the expedited reporting criteria as 
outlined in Section 16.0 of the protocol must be reported to the Operations Office, Study 
Chair and NCI via CTEP-AERS, and to the IRB per local IRB requirements.

CLOSED EFFECT
S
CTIVE 10/01/2015
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Revised 11/22/13
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NOTE: Timing of the follow-up assessments are based on the start date of protocol treatment.
Click here to see footnotes. 
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Revised 11/22/13
S1202
Page 29
Version Date 1/19/15
Footnotes
Į
Patient reported questionnaires and blood draw must be completed prior to starting blinded drug.
ȍ
On Day 15, review only the intake calendar and record AI adherence in the patient record. Do not perform pill count. See Section 7.2b.
į
Adverse events will be collected on the phone call.  Report adverse events on the 6 Adverse Event Summary Form. Phone call must be 
completed within +/- 2 days from Day 99.

See Section 15.1.
†
Assessments must be completed during Day 15-21. 
ʌ
Assessments must be completed during Day 40-46.
¥
Assessments must be completed during Day 79-85.
Ԝ
Assessments must be compeleted within +/- 7 days from Day 169.
ȕ
After the pill count, return enough pills to the patient to complete the Day 85-91 taper. See Section 7.2b.

Administer questionnaires at the scheduled assessments even if the patient goes off protocol treatment prior to Day 85 for any reason. 
6 Cover Sheet for Completed Questionnaires must be completed and included with the submission of patient questionnaires. See
Section 7.2 and 15.2.
º
Patient is to take study drug daily. See Section 7.1.
*
A statement that musculoskeletal symptoms started or worsened since initiation of adjuvant AI therapy must be documented in the patient’s 
medical record at prestudy.
~
Must be performed within 28 days prior to registration.
CLOSED EFFECTIVE 10/01/2015
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10.1 
Primary Outcome
Reduction in 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” (assessed at Weeks 2, 6 and 
12).
10.2
Main Secondary Outcome 
Reduction in worst joint pain according to the BPI-SF worst pain score (item #2) at 12 
weeks. This item has a scale of 0 to 10 with 0 indicating “No pain” and 10 indicating “Pain 
as bad as you can imagine”. 
10.3
Performance Status
Participants will be graded according to the Zubrod performance status scale.
POINT
DESCRIPTION
0 
Fully active, able to carry on all pre-disease performance without 
restriction.
1 
Restricted in physically strenuous activity but ambulatory and 
able to carry out work of a light or sedentary nature, e.g., light 
housework, office work.  
2 
Ambulatory and capable of self-care but unable to carry out any 
work activities; up and about more than 50% of waking hours.  
3 
Capable of limited self-care, confined to bed or chair more than 
50% of waking hours.  
4 
Completely disabled; cannot carry on any self-care; totally 
confined to bed or chair.  

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11.1
Primary Objective
Joint pain will be assessed using “average pain” according to the BPI-SF. Enrollees must 
currently be taking AIs and must exhibit joint pain with a minimum BPI-SF average pain 
score of 4; scores of 4 to 10 are considered to reflect moderate to severe pain. (42)
Patients will be stratified at randomization by the use of average baseline pain according 
to the BPI (4-6 vs 7-10) and prior taxane use (yes vs. no). The primary assessment time
of 12 weeks, upon which power calculations are based, corresponds to completion of the 
intervention and allows cross-trial comparisons to be made with 6, which is 
evaluating a different pharmacologic agent for treatment of AIMSS in the same patient 
population.
This study stipulates an alpha=.05 two-sided test, with an estimated 5% non-adherence 
(reducing the nominal effect size) and 15% dropout rate (increasing the total required 
sample size) at 12 weeks after randomization. (16, 43) In addition, the design will 
PI-
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N
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S1202 
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incorporate a 10% contamination rate (which also reduces the nominal effect size) based 
on the assumption that a portion of the patients will not benefit from intervention based on 
joint pain with a different etiology that is not associated with AI treatment (this has a
similar impact on power calculations as a “drop-in” rate).(44)  
The proposed sample size incorporates adjustments for loss, non-adherence, and 
contamination. The power for the design will be a function of the difference detected and 
the standard deviation at 12 weeks after randomization. 
Difference Detected: Although a difference of 2 points in the BPI has been identified as 
representing a clinically meaningful individual level difference, for power calculations 
assessing group-level differences, we will test a smaller effect. (45) Specifically, an 
incremental difference in pain reduction due to duloxetine over placebo of about 1.0 
points at 12 weeks has been repeatedly found in the setting of fibromyalgia. (43,46) 
Standard Deviation: Multiple studies of AI-induced joint pain have found the standard 
deviation for BPI “average pain” at follow-up on placebo to be about 2.0 to 2.5 points.
(47,8) The design assumes a common standard deviation between arms; a similar 
standard deviation has been observed in a pilot study of duloxetine.  (16) We assume a 
SD of 2.3 points at 12 weeks for this study (the estimated average SD found in Arnold, 
Clin J Pain, 2009). (8)
For a 1.0 point difference and a 2.3 point SD at 12 weeks, with other parameters as 
specified above, 270 eligible patients would be required for 80% power under a two-arm 
normal design. Power will be higher with lower observed standard deviation or a larger 
observed difference.  
The following considerations clarify the impacts of loss, non-adherence, and 
contamination on the sample size calculations:
x
A two-arm normal design with alpha=.05 two-sided test and a 2.3 point SD to 
detect a difference of 1.0 points requires approximately 166 patients (83 per arm) 
for 80% power.
x
An estimated 5% non-adherence and 10% contamination both reduce the 
nominal effect size, from 1.0 points to 0.85 points. This increases the required 
sample size to 230 total patients (115 per arm).
x
To account for an estimated 15% dropout rate, the total required sample size 
must be further increased by 15%, as in 230/0.85 = 270 total patients.
The primary analysis will rely on longitudinal measures of BPI at Weeks 2, 6, and 12 for 
improved power. (Thus the proportion or patients with zero follow-up observations will 
likely be less than the specified 5% non-adherence and 15% dropout at 12 weeks used 
for power calculations.) Assessment windows of +/- 7 days, +/- 14 days, and +/- 14 days 
will be allowed for the 2, 6, and 12 week timepoints. (Given the primary analysis is based 
on longitudinal measures, a sensitivity analysis will consider all observations within 14 
weeks of registration.)  The analysis will be performed using mixed models, adjusted for 
baseline average pain and the stratification factors. To minimize missed assessments, 
SWOG utilizes an electronic system to remind institutions in real-time that patients are 
due for follow-up assessment. If the proportion of missing follow-up data is >20% (the 
sum of the specified targets for non-adherence and dropout), plots of mean pain levels 
over time for patients grouped by number of follow-up responses will be examined to 
check for patterns of informative missing data. Should these plots suggest that data may 
not be missing at random, pattern mixture models, which models missingness patterns 
through stratification, will be utilized for analysis of the longitudinal BPI pain data. (48, 49)
and 
an
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Under the intention-to-treat principle, the primary analysis will be based on all eligible, 
randomized patients. To allow for an ineligibility rate of 8%, as found on our recent 
Symptom Control study 6, a total of 294 patients will be enrolled to achieve 270
eligible patients.  
11.2 
Accrual Monitoring
Accrual is expected to be rapid given the common use of AIs for adjuvant therapy in 
postmenopausal women with breast cancer. Allowing for 6 months ramp-up and IRB 
approval time, accrual of 15 patients/month would allow completion of the study in 
approximately 2 years. Accrual will be assessed at 1.5 years after study activation. If 
monthly average accrual in quarters 5-6 after study activation is < 50% of projected 
accrual, efforts will be made to increase accrual over the succeeding 6 month period. If 
after 2 years, monthly accrual remains < 50% of projected accrual, study revision will be 
considered.
11.3
Secondary Endpoints
The following secondary analyses will be conducted:
a.
Multiple linear regression analyses of the individual assessment timepoints will 
be conducted to identify potential critical effectiveness timepoints and to allow 
comparisons to other studies. These analyses will include the baseline score (as 
a covariate) as well as the pre-specified stratification factors.
b.
At weeks 2, 6, and 12, we will investigate whether duloxetine 60 mg daily: 
1. 
Decreases worst joint pain according to the BPI. 
2. 
Improves functioning, pain, and stiffness in the knees/hips according to 
the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) 
scale. Differences between the two study arms of at least two points on 
the WOMAC Index are of interest. (50, 51) We will also evaluate clinically
meaningful change for the WOMAC Index with respect to the ѿ to ½
standard deviation during the study period of 12 weeks.  
3.
Improves function, pain and stiffness in the hands according to the 
Modified Score for the Assessment and Quantification of Chronic 
Rheumatoid Affections of the Hands (M-SACRAH). Differences between 
the two study arms of at least two points on the M-SACRAH are of 
interest. (50,51) We will also evaluate clinically meaningful change for 
the M-SACRAH with respect to the ѿto ½ standard deviation during the 
study period of 12 weeks. 
4.
Improves functional quality of life as measured by the Functional 
Assessment of Cancer Therapy-Endocrine Scale (FACT-ES).(52,53)
Trial Outcome Index (TOI). Clinically meaningful change in FACT-ES TOI 
scores will also be based on ѿto ½ of a standard deviation. (53-55)
5.
Improves the proportion of patients reporting changes for the better 
versus worst as measured by the Global Rating of Change Scale. The 
GRCs for joint pain and for joint stiffness will be used to identify patients 
who report they are worse (combining scores of -1 through -3), the same 
score (score of 0), or better (combining scores of +1 through +3) since 
the last time they completed the questionnaire. (54-56) Mean scores for 
the WOMAC Index, BPI, M-SACRAH, and FACT-ES TOI will be 
compared for groups based on those patients who select “a little better” 
and “a little worse” on the GRC ratings to identify minimally important 
change. (54-56) 
CLOSED EFFECTIVE 10/01/2015
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6.
Reduces depression as measured by the Patient Health Questionnaire 
(PHQ-9). Differences between the two arms of at least five points on the 
PHQ-9 at 12 weeks will be of interest. (57) Clinically meaningful change 
in PHQ-9 scores will also be based on ѿto ½ of a standard deviation.
(57) 
7.
Decreases analgesic use. 
8.
Increases adherence to, and reduces the discontinuation rate for, AI 
therapy. 
9.
Affects measures of pain interference. 
10.
Reasons for treatment discontinuation will also be described.   
c.
Interaction tests between treatment and stratification variables will be conducted 
to explore whether these factors are predictive of average pain scores.
d.
A logistic regression analysis of responders will be conducted, where a response 
to intervention is defined as a reduction of 2 or more points in average pain 
according to the BPI. (50)
e.
In addition, we will explore the relationship between the severity of arthralgias 
and degree of benefit from therapy in each of the treatment groups and inherited 
variants in genes responsible for duloxetine metabolism and activity (COMT, 
HTR3A, SLC6A2, SLC6A4, CYP1A2, CYP2D6) and aromatase (CYP19A1). 
Finally, we will explore the relationship between baseline and change in serum 
inflammatory cytokine levels with 12 weeks of treatment and the degree of 
benefit from therapy in each of the treatment groups. 
For linear scales, secondary endpoints will be analyzed using multiple linear 
regression analyses including the baseline score as a covariate and the pre-
specified stratification factors. For binary outcomes, logistic regression will be 
used.  
11.4
Data and Safety Monitoring Committee
A Data and Safety Monitoring Committee will oversee the conduct of the study.  The 
Committee consists of four members from outside of the SWOG, 3 SWOG members, 3 
non-voting representatives from the National Cancer Institute (NCI), and the Group 
Statistician (non-voting).  The members of this Committee will receive confidential reports 
every 6 months from the SWOG Statistical Center, and will meet at the Group's bi-annual 
meetings as necessary.  The Committee will be responsible for decisions regarding 
possible termination and/or early reporting of the study. Given the anticipated rapid 
accrual to this protocol ( 2 years total), insufficient data will be available while the study 
is still accruing to conduct an interim analysis. Thus no formal interim analysis is planned.

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Revised 9/18/13
S1202
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13.1
Registration Timing
Patients must be registered prior to initiation of treatment (no more than five working days 
prior to planned start of treatment).  
13.2
Investigator/Site Registration
Prior to the recruitment of a patient for this study, investigators must be registered 
members of a Cooperative Group.  Each investigator must have an NCI investigator 
number and must maintain an “active” investigator registration status through the annual 
submission of a complete investigator registration packet (FDA Form 1572 with original 
signature, current CV, Supplemental Investigator Data Form with signature and Financial 
Disclosure Form with original signature) to the Pharmaceutical Management Branch, 
CTEP, DCTD, NCI.  These forms are available on the CTSU Web site (enter credentials 
at https://www.ctsu.org; then click on the Register tab) or by calling the PMB at 240/276-
6575 Monday through Friday between 8:30 a.m. and 4:30 p.m. Eastern time.
Each investigator or group of investigators at a clinic site must obtain IRB approval for 
this protocol and submit IRB approval and supporting documentation to the CTSU 
Regulatory Office before they can enroll patients.  Study centers can check the status of 
their registration packets by querying the Regulatory Support System (RSS) site 
registration status page of the CTSU member web site by entering credentials at 
https://www.ctsu.org.
Requirements for site registration:
x
CTSU IRB Certification
x
CTSU IRB/Regulatory Approval Transmittal Sheet
13.3
OPEN Registration Requirements
The individual registering the patient must have completed the appropriate SWOG 
Registration Worksheet.  The completed form must be referred to during the registration 
but should not be submitted as part of the patient data.
OPEN will also ask additional questions that are not present on the SWOG Registration 
Worksheet.  The individual registering the patient must be prepared to provide answers to 
the following questions:
a.
Institution CTEP ID
b.
Protocol Number
c.
Registration Step
d.
Treating Investigator
e.
Cooperative Group Credit
f.
Credit Investigator
g.
Patient Initials
h.
Patient’s Date of Birth
CLOSED EFFECTIVE 10/01/2015
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Revised 9/18/13
S1202
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Version Date 1/19/15
i.
Patient SSN (SSN is desired, but optional.  Do not enter invalid numbers.)
j.
Country of Residence
k.
ZIP Code
l.
Gender (select one):
x
Female Gender
x
Male Gender
m.
Ethnicity (select one):
x
Hispanic or Latino
x
Not Hispanic or Latino
x
Unknown
n.
Method of Payment (select one):
x
Private Insurance
x
Medicare
x
Medicare and Private Insurance
x
Medicaid
x
Medicaid and Medicare
x
Military or Veterans Sponsored NOS
x
Military Sponsored (Including Champus & Tricare)
x
Veterans Sponsored
x
Self Pay (No Insurance)
x
No Means of Payment (No Insurance)
x
Other
x
Unknown
o.
Race (select all that apply):
x
American Indian or Alaska Native
x
Asian
x
Black or African American
x
Native Hawaiian or other Pacific Islander
x
White
x
Unknown
13.4 
Registration procedures 
a.
All site staff will use OPEN to enroll patients to this study.  OPEN is a web-based 
application and can be accessed at https://open.ctsu.org, or from the OPEN tab 
on the CTSU members’ side of the website at https://www.ctsu.org, or from the 
OPEN Patient Registration link on the SWOG CRA Workbench.  
b.
Prior to accessing OPEN site staff should verify the following:
x
All eligibility criteria have been met within the protocol stated 
timeframes. Site staff should refer to Section 5.0 to verify eligibility.
x
All patients have signed an appropriate consent form and HIPAA 
authorization form (if applicable).  
  
CLOSED EFFECTIVE 10/01/2015
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c.
Access requirements for OPEN:
  
x
Site staff will need to be registered with CTEP and have a valid and 
active CTEP-IAM account. This is the same account (user ID and 
password) used for the CTSU members' web site. 
x
To perform registrations on SWOG protocols you must have an 
equivalent 'Registrar' role on the SWOG roster.  Role assignments are 
handled through SWOG. 
Note:  The OPEN system will provide the site with a printable confirmation of 
registration and treatment information.
Please print this confirmation for your 
records.
d.
Further instructional information is provided on the OPEN tab on the CTSU 
members’ side of the website at https://www.ctsu.org or at https://open.ctsu.org. 
For any additional questions contact the CTSU Help Desk at 1-888-823-5923 or 
ctsucontact@westat.com.
13.5 
Exceptions to SWOG registration policies will not be permitted.
a.
Patients must meet all eligibility requirements.
b.
Institutions must be identified as approved for registration.
c.
Registrations may not be cancelled.
d.
Late registrations (after initiation of treatment) will not be accepted.

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14.1
Data Submission Requirement
Data must be submitted according to the protocol requirements for $// patients 
registered, whether or not assigned treatment is administered, including patients deemed 
to be ineligible.  Patients for whom documentation is inadequate to determine eligibility 
will generally be deemed ineligible.
14.2
Master Forms

0DVWHU IRUPV can be found on the protocol abstract age on the SWOG website 
(www.swog.org) and (with the exception of the sample consent form and the Registration 
Worksheet) must be submitted on-line via the Web; see Section 14.3a for details.  
14.3
Data Submission Procedures 
a.
SWOG institutions must submit data electronically via the Web using Medidata 
Rave® at the following url:
https://login.imedidata.com/selectlogin
1.
If prompted, select the ‘CTEP-IAM IdP’ link.
2.
Enter your valid and active CTEP-IAM userid and password.  This is the 
same account used for the CTSU members’ web site and OPEN.
CLOSED EFFECTIVE 10/01/2015
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14.3
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b.
You may also access Rave® via the SWOG CRA Workbench. Go to the SWOG 
web site (http://swog.org) and logon to the Members Area using your SWOG 
Roster ID Number and password. After you have logged on, click on 
Workbenches, then CRA Workbench to access the home page for the CRA 
Workbench and follow the link to Rave® provided in the left-hand navigation 
panel.
To access the CRA Workbench the following must be done (in order):
1.
You are entered into the SWOG Roster and issued a SWOG Roster ID 
Number,
2.
You are associated as an investigator or CRA/RN at the institution where
the patient is being treated or followed, 
3.
Your Web User Administrator has added you as a web user and has 
given you the appropriate system permissions to view data for that 
institution. 
For assistance with points 1 and 2 call the Operations Office at 210/614-8808.  
For point 3, contact your local Web User Administrator (refer to the "Who is my 
Web User Administrator?" function on the swog.org Members logon page). 
For 
difficulties 
with 
the 
CRA 
Workbench, 
please 
email 
technicalquestion@crab.org. 
c.
Institutions participating through Cancer Trials Support Unit (CTSU) please refer 
to the CTSU Participation Table on Page 4. 

14.4
Data Submission Overview and Timepoints

a.
AFTER REGISTRATION BUT PRIOR TO BEGINNING PROTOCOL 
TREATMENT: 
Submit baseline whole blood for DNA and blood for serum biomarkers as 
outlined in Section 15.1. The SWOG Specimen Tracking System must be used 
for specimen submission. 

b.
WITHIN 7 DAYS OF REGISTRATION:
Submit the following:
6 Onstudy Form 
6 Cover Sheet for Patient-Completed Questionnaires 
6 Brief Pain Inventory Short Form (BPI-SF) 
6 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) 
Index (Version 3.1) 
6 Modified-Score for the Assessment and Quantification of Chronic 
Rheumatoid Affections of the Hands (M-SACRAH) 
6 FACT-ES Trial Outcome Index (Version 4) 
6 Patient Health Questionnaire-9 (PHQ-9)
Institutional surgical pathology report to confirm diagnosis of ER/PgR status
CLOSED EFFECTIVE 10/01/2015
n 
OG Roster ID
OG Roster I
e institution w
nstitution w
s a web user
s a web use
ns to view da
ns to view d
erations Offic
ations Off
ministrator (re
nistrator (r
wog.org Mem
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CRA 
Wor
CRA 
h Cancer Tria
h Cancer Tria
able on 
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Page 
TIV
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Timepoints
RATION BUT 
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Revised 9/18/13
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Version Date 1/19/15
c.
WITHIN 14 DAYS OF DAY 15, 43, 85 STUDY ASSESSMENTS: 
Submit the following:
6 Treatment Form 
6 Adverse Event Summary Form 
6 Supplemental Agents Reporting Form  
6 Cover Sheet for Patient-Completed Questionnaires 
6 Brief Pain Inventory Short Form (BPI-SF) 
6 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) 
Index (Version 3.1)  
6 Modified-Score for the Assessment and Quantification of Chronic 
Rheumatoid Affections of the Hands (M-SACRAH) 
6 FACT-ES Trial Outcome Index (Version 4) 
6 Global Ratings of Change in Joint Pain and Stiffness 
d.
WITHIN 14 DAYS OF DAY 43 AND 85 ASSESSMENTS: 
In addition to the forms listed in Section 14.4c, submit the 6 Patient Health 
Questionnaire-9 (PHQ-9)
e.
WITHIN 14 DAYS OF DAY 85 ASSESSMENT: 
In addition to the forms listed in Sections 14.4c and 14.4d, submit the 6
Patient Treatment Satisfaction Form
f.
AT THE DAY 85 STUDY ASSESSMENT: 
Submit blood for serum biomarkers as outlined in Section 15.1. The SWOG 
Specimen Tracking System must be used for specimen submission. 
g. 
WITHIN 14 DAYS OF THE DAY 99 TELEPHONE CALL TO PATIENT: 
Submit the 6 Adverse Event Summary
h. 
WITHIN 14 DAYS OF THE DAY 169 FINAL STUDY ASSESSMENT: 
Submit the following:
6 Supplemental Agents Reporting Form 
6 Cover Sheet for Patient-Completed Questionnaires 
6 Brief Pain Inventory Short Form (BPI-SF)  
6 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) 
Index (Version 3.1) 
CLOSED EFFECTIVE 10/01/2015
Osteoarthritis (
steoarthritis 
nd Quantifica
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4
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Revised 9/18/13
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Version Date 1/19/15
6 Modified-Score for the Assessment and Quantification of Chronic 
Rheumatoid Affections of the Hands (M-SACRAH) 
6 FACT-ES Trial Outcome Index (Version 4) 
6 Global Ratings of Change in Joint Pain and Stiffness 
i. 
WITHIN 14 DAYS OF REMOVAL FROM PROTOCOL INTERVENTION: 
Submit the following:
Off Treatment Notice-Prevention Studies 
Final 6 Treatment Form 
Final 6 Adverse Event Summary 
Final 6 Supplemental Agents Reporting Form
NOTE: If the patient goes off protocol intervention prior to Day 91 for any reason 
(see Section 7.4), the 6 Supplemental Agents Reporting Form and the 
patient-completed questionnaires should continue to be administered according 
to the protocol assessment schedule.
j. 
WITHIN 14 DAYS OF A DIAGNOSIS OF NEW OR RECURRENT CANCER 
OCCURING UP TO DAY 169 ASSESSMENT:
Submit the Follow-up Form. 
NOTE: If the patient was on protocol intervention at the time of new or recurrent 
cancer diagnosis then also submit the forms listed in Section 14.4i.
k. 
WITHIN 4 WEEKS OF KNOWLEDGE OF DEATH OCCURING UP TO 168 
DAYS AFTER REGISTRATION: 
If patient was on 6 protocol intervention, submit: 
Notice of Death documenting death information
6 Treatment Form 
6 Adverse Event Summary 
6 Supplemental Agents Reporting Form 
If patient was off 6 protocol intervention, submit: 
Notice of Death documenting all death information

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15.1
Correlative Studies and Banking 
Specimens for correlative studies and banking (submitted to the SWOG Specimen 
Repository – Solid Tissue, Myeloma and Lymphoma Division, Lab #201) (required for 
patient):
CLOSED EFFECTIVE 10/01/2015
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Version Date 1/19/15
Revised 1/19/15
a.  
Specimens must be submitted at the following times ** (see Section 9.0):
1.
6 cc of whole blood for DNA at baseline*
2.
10 cc of blood for serum at baseline* and Day 85
* Baseline specimens must be obtained after registration, but before the start of 
protocol treatment.
**With patient consent, leftover specimens will be banked for future unknown 
use.
b.
Specimen collection and submission instructions can be accessed on the SWOG 
Specimen Submission webpage
(http://swog.org/Members/ClinicalTrials/Specimens/STSpecimens.asp), or via the 
link on the 6protocol abstract page on the SWOG website (www.swog.org).
c.
Specimen collection kits are not being provided for this study; sites will use 
institutional supplies.
15.2
Patient Questionnaires: Instructions for Administration
a.
It is important to note that the time frame for providing ratings differs depending 
on the scale the patient is completing. The 6 BPI-SF, 6 WOMAC 
Index, 6 M-SACRAH, 6 FACT-ES TOI, and 6 PHQ-9 should be 
rated with respect to the past 7 days. The 6 Global Ratings of Change in
Joint Pain and Joint Stiffness are answered with respect to the last time the 
patient filled out the questionnaire.
If treatment is delayed for any other reason, the assessment schedule for the 
Day 15, 43, 85, and 168 assessments should be defined from the treatment start 
date. 
b.
Administration of Questionnaires
1.
The first time the patient completes the questionnaires: Please read to 
the patient the instructions attached to each patient questionnaire.  
Explain the specific administration times for this protocol.  Patients 
should be directed to report all symptoms and limitations whether or not 
they are related to the cancer or its treatment.
2.
It is permissible to assist patients with completing the questionnaires 
being careful not to influence the patient's response.  Note on the 6
Cover Sheet for Patient-Completed Questionnaires what assistance was 
required and indicate reason (e.g., elderly, too sick, etc.).  Discourage 
family members from: 1) being present while the patient completes the 
questionnaire and/or 2) influencing patient responses to the questions.
3.
It is very important to review the questionnaires after the patient has 
completed them to be sure all of the questions have been answered and 
that only one answer is marked.  a) If the patient has marked more than 
one answer per question, ask the patient which answer reflects how she 
is feeling.  b) If the patient has skipped a question, tell the patient that a 
question was not answered and ask if she would like to answer the 
question.  Always give the patient the option to refuse.  Indicate on the 
form by the question that the patient did not want to answer this 
question.
CLOSED EFFECTIVE 10/01/2015
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Revised 1/19/15
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Version Date 1/19/15
4.
If a patient refuses or cannot complete the questionnaire for some 
reason, then this must be documented on the 6 Cover Sheet for 
Patient Completed Questionnaires and submitted to the Data Operations 
Center in Seattle (see Section 14.3). 
5.
If a patient misses an appointment or is too sick to complete the 
questionnaires on the scheduled date, the questionnaire can be mailed 
to the patient or sent home with her.  A telephone interview must be 
scheduled and completed within one week of the originally scheduled 
time.  Patient responses to questionnaire items are to be obtained during 
the telephone interview while the patient is looking at her copy of the 
questionnaire.  
c.  
Additional quality control procedures:
1.
When a patient is registered on 6, a calendar should be made with 
dates of upcoming patient-completed questionnaires noted.  A copy of 
this calendar can be given to the patient with the notation that the 
questionnaires should be completed before receiving treatment.  You 
may wish to photocopy the Study Calendar, Section 9.0, and include the 
patient's name and specific dates.  A copy of this should be kept in the 
patient file.
2.
If a patient goes off study intervention prior to the protocol-defined end of 
intervention at 85 days, administer the patient-completed questionnaires 
according to the protocol-defined assessment schedule (timed from the 
treatment start date).
3.
If a patient refuses or cannot complete the patient questionnaires at one 
time point, she should be asked to do so at the next scheduled 
administration time.
Submit the 6
Cover Sheet for Patient-
Completed 
Questionnaires 
documenting 
the 
reason 
why 
the 
questionnaires were not done.
4.
Anyone involved in the collection of quality of life data in SWOG trials 
should review the training program available on the SWOG website
accessible from three locations. On the SWOG Home Page (prior to 
member login), in the 48,&./,1.6 section on the bottom right corner of 
the page, there is a link to the Patient Reported Outcomes Training. The 
other two locations that the training is available are after SWOG member
login on the CRA Workbench. The Training section and the New CRAs!
Section both contain access to the Patient Reported Outcomes (PROs) 
training module. The training program is a narrated set of slides 
designed to standardize the way quality of life data is collected from 
patients. Questions regarding the quality of life assessments can be 
addressed to Dr. Henry (734/936-4991) or the SWOG Data Operations 
Office (206/652-2267).    
d.
6Cover Sheet for Patient-Completed Questionnaires
For each time point, the nurse or CRA completes the 6 Cover Sheet for
Patient-Completed Questionnaires.  The Cover Sheet is submitted with the set of 
patient-completed forms at each scheduled assessment.  The Cover Sheet is 
very important for tracking how and when the patient forms were completed.  
When a patient-completed form is not administered at a scheduled time point, it 
CLOSED EFFECTIVE 10/01/2015
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Revised 11/22/13
S1202
Revised 4/29/14
Page 42
Version Date 1/19/15
is important to know why the assessment did not occur; the form includes 
potential reasons for a patient not completing a form.  See Section 14.0 for data 
submission guidelines.
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The following must be observed to comply with Food and Drug Administration regulations for the 
conduct and monitoring of clinical investigations; they also represent sound research practice:
Informed Consent
The principles of informed consent are described by Federal Regulatory Guidelines (Federal 
Register Vol. 46, No. 17, January 27, 1981, part 50) and the Office for Protection from Research 
Risks Reports:  Protection of Human Subjects (Code of Federal Regulations 45 CFR 46).  They 
must be followed to comply with FDA regulations for the conduct and monitoring of clinical 
investigations.
Institutional Review
This study must be approved by an appropriate institutional review committee as defined by 
Federal Regulatory Guidelines (Ref. Federal Register Vol. 46, No. 17, January 27, 1981, part 56) 
and the Office for Protection from Research Risks Reports:  Protection of Human Subjects (Code 
of Federal Regulations 45 CFR 46).
Monitoring
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.  
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are 
due January 31, April 30, July 31 and October 31.
Confidentiality
Please note that the information contained in this protocol is considered confidential and should 
not be used or shared beyond the purposes of completing protocol requirements until or unless 
additional permission is obtained.
16.1
Adverse Event Reporting Requirements  
a.
Purpose
Adverse event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled in the studies as 
well as those who will enroll in future studies using similar agents. Adverse 
events are reported in a routine manner at scheduled times during a trial. 
(Directions for routine reporting are provided in Section 14.0.) Additionally, 
certain adverse events must be reported in an expedited manner to allow for 
more timely monitoring of patient safety and care. The following guidelines 
prescribe expedited adverse event reporting for this protocol. See also Appendix 
18.1 for general and background information about expedited reporting.
b.
Reporting method
This study requires that expedited adverse event reporting use CTEP’s Adverse 
Event Reporting System (CTEP-AERS).  The NCI’s guidelines for CTEP-AERS
can be found at
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adverse_ev
ents.htm.
CLOSED EFFECTIVE 10/01/2015
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Revised 11/22/13
S1202
Revised 4/29/14
Page 43
Version Date 1/19/15
In the rare event when internet connectivity is disrupted an electronic report 
MUST be submitted immediately upon re-establishment of internet connection.  
c.
When to report an event in an expedited manner
When the adverse event requires expedited reporting, submit the report within 10 
calendar days of learning of the event.
d.
Other recipients of adverse event reports
The SWOG Operations Office will forward reports and documentation to the 
appropriate regulatory agencies and drug companies as required. 
Adverse events determined to be reportable to the Institutional Review Board 
responsible for oversight of the patient must be reported according to local policy 
and procedures. 
e.
Expedited reporting for commercial agents
Commercial reporting requirements are provided in Table 16.1. The commercial 
agent used in this study is duloxetine. If there is any question about the 
reportability of an adverse event or if on-line CTEP-AERS cannot be used, 
please telephone or email the SAE Program at the Operations Office, 210/614-
8808 or adr@swog.org, before preparing the report.
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days after the last dose of treatment with a commercial agent(s) and is attributed 
(possibly, probably, or definitely) to the agent(s) and is not due to cancer 
recurrence must be reported according to the instructions above.

E Submission of the on-line CTEP-AERS report plus any necessary amendments 
generally completes the reporting requirements. You may, however, be asked to 
submit supporting clinical data to the Operations Office in order to complete the 
evaluation of the event. If requested, the specified data should be sent within 5 
calendar days by fax to 210-614-0006.
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
1.
American Cancer Society: Breast Cancer Facts and Figures, 2007-2008. Available at: 
http://www.cancer.org/downloads/STT/BCFF-Final.pdf. Accessed February 12, 2008. 
2.
Crew KD, Greenlee H, Capodice J, et al. Prevalence of joint symptoms in postmenopausal 
women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25:3877-83, 2007
3. 
Henry NL, Giles JT, Stearns V. Aromatase inhibitor-associated musculoskeletal symptoms: 
etiology and strategies for management. Oncology (Williston Park) 22:1401-8, 2008
4. 
Henry NL, Giles JT, Ang D, et al. Prospective characterization of musculoskeletal symptoms in 
early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 
111:365-372, 2008
 
 
5.
Henry NL, Azzouz F, Desta Z, et al. Predictors of aromatase inhibitor discontinuation due to 
treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol, epub Feb 13, 2012. 
 
 
6.
Crew KD, Capodice J, Greenlee H, et al, Randomized, blinded, sham-controlled trial of 
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7.
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13.
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Chalon S, Pereira A, Lainey E, et al, Comparative effects of duloxetine and desipramine on sleep 
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sal 
al 
007
07
ymptoms:
ymptoms:
etal symptom
al symptom
t Cancer Res
Cancer Res
itor discontinu
or discon
Oncol, epub Fe
Oncol, epub F
blinded, sha
blinded, sha
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ciated join
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riso
risons of the e
ns of the 
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Desaiah D, Liu
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ack pain. Spin
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ski V, Desaia
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chronic low 
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Cymba
Cymba
15.
Br
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in 
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of diabet
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duloxetine response in a clinical trial for major depressive disorder. Biol Psychiatry 65:785-91, 
2009. 
 
 
38. 
Yoshida K, Higuchi H, Takahashi H, et al, Influence of the tyrosine hydroxylase val81met 
polymorphism and catechol-O-methyltransferase val158met polymorphism on the antidepressant 
effect of milnacipran. Hum Psychopharmacol 23:121-8, 2008. 
 
 
39. 
Mao JJ, Su HI, Feng R, et al, Association of functional polymorphisms in CYP19A1 with 
aromatase inhibitor associated arthralgia in breast cancer survivors. Breast Cancer Res 13:R8, 
2011. 
 
 
40. 
Park IH, Lee YS, Lee KS, et al, Single nucleotide polymorphisms of CYP19A1 predict clinical 
outcomes and adverse events associated with letrozole in patients with metastatic breast cancer. 
Cancer Chemother Pharmacol, 2011. 
 
 
41. 
Fornaro M, Martino M, Battaglia F, et al, Increase in IL-6 levels among major depressive disorder 
patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation.
Neuropsychiatr Dis Treat 7:51-6, 2011. 
 
 
42. 
Serlin RC, Mendoza TR, Nakamura Y, et al, When is cancer pain mild, moderate or severe? 
Grading pain severity by its interference with function. Pain 61:277-84, 1995. 
43.
Arnold LM, Rosen A, Pritchett YL, D’Souza DN, Goldstein DJ, Iyengar S, Wernicke JF. A 
randomized, double-blind, placebo-controlled trial of duloxetine in the treatment of women with 
fibromyalgia with or without major depressive disorder. Pain 119(1-3):5-15, 2005.
44.
Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes 
ED, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. 
The influence of finasteride on the development of prostate cancer. N Engl J Med 349(3):215-24, 
2003.
45.  
Dworkin R, et al. Interpreting the clinical importance of group differences in chronic pain clinical 
trials: IMMPACT recommendations. Pain 146(3):238-44, 2009.
46.
Arnold LM, Lu Y, Crofford LJ, Wohlreich M, Detke MJ, Iyengar S, Goldstein DJ. A double-blind, 
multipcenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with 
or without major depressive disorder. Arthritis Rheum 50(9):2974-84, 2004.
47. 
Crew KD, Capodice JL, Greenlee H, Brafman L, Fuentes D, Awad D, Yann Tsai W, Hershman 
DL. Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase 
inhibitor-associated joint symptoms in women with early-stage breast cancer. J Clin Oncol 
28(7):1154-60, 2010.
48.
Little RJ, Wang Y. Pattern-mixture models for multivariate incomplete data with covariates. 
Biometrics 52(1):98-11, 1996.
CLOSED EFFECTIVE 10/01/2015
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ity in 
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rosine hydrox
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49.
Pauler DK, McCoy S, Moinpour C. Pattern mixture models for longitudinal quality of life studies in 
advanced stage disease. Stat Med 22(5):795-809, 2003.
50.
Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in 
chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 94:149-158, 
2001.
51. 
Sautner J, Andel I, Rintelen B, et al. Development of the M-SACRAH, a modified, shortened 
version of SACRAH (Score for the Assessment and Quantification of Chronic Rheumatoid 
Affections of the Hands). Rheumatology (Oxford) 43:1409-13, 2004.
52. 
Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment of Cancer Therapy Scale: 
Development and validation of the general measure. J Clin Onc 11:570-79, 1993. 
53.
Fallowfield LJ, Leaity SK, Howell A, et al. Assessment of quality of life in women undergoing 
hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACTB. 
Breast Cancer Res Treat 55:189-99, 1999.
54. 
Hu FB, Bronner L, Willett WC, Stampfer MJ, Rexrode KM, Albert CM, Hunter D, Manson JE.  Fish 
and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA; 287(14):1815-
1821, 2002. 
55. 
Yost KJ, Sorensen MV, Hahn EA, Glendenning GA, Gnanasakthy A, Cella D. Using multiple 
anchor-and distribution-based estimates to evaluate clinically meaningful change on the 
Functional Assessment of Cancer Therapy-Biologic Response Modifiers (FACT-BRM) instrument. 
Value Health 8:117-127, 2005.
56. 
Fallowfield L, Cella D, Cuzick J, Francis S, Locker G, Howell A. Quality of life postmenopausal 
women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) adjuvant breast cancer trial. 
J Clin Oncol 22:4261-4271, 2004. 
57. 
Lowe B, Unutzer J, Callahan C, Perkins AJ, Kurt K. Monitoring depressing treatment outcomes 
with the Patient Health Questionnaire-9. Med Care 42(12):1194-1201, 2004.
CLOSED EFFECTIVE 10/01/2015
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Determination of Expedited Adverse Event Reporting Requirements
18.2
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18.3
Guidelines for Emergency Unblinding of Coded Drug
18.4
IND Exemption Let
CLOSED EFFECTIVE 10/01/2015


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Page 49
Version Date 1/19/15
18.1
Determination of Expedited Adverse Event Reporting Requirements
Adverse event data collection and reporting, which are required as part of every clinical 
trial, are done to ensure the safety of patients enrolled in the studies as well as those who 
will enroll in future studies using similar agents. Adverse events are reported in a routine 
manner at scheduled times during a trial. (Directions for routine reporting are provided in 
Section 14.0.) Additionally, certain adverse events must be reported in an expedited 
manner to allow for more timely monitoring of patient safety and care. Expedited adverse 
event reporting principles and general guidelines follow; specific guidelines for expedited 
adverse event reporting on this protocol are found in Section 16.1.
All serious adverse events determined to be reportable to the Institutional Review Board 
responsible for the oversight of the patient must be reported according to local policy and 
procedures.  Documentation of this reporting should be maintained for possible 
inspection during quality assurance audits.
Steps to determine if an adverse event is to be reported in an expedited manner 
(This includes all events that occur while on treatment or within 30 days of the last dose 
of protocol treatment.)
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6WHS Determine whether the patient has received an investigational agent, commercial 
agent, or a combination of investigational and commercial agents.

$QLQYHVWLJDWLRQDODJHQW is a protocol drug administered under an Investigational New 
Drug Submission (IND). In some instances, the investigational agent may be available 
commercially, but is actually being tested for indications not included in the approved 
package label. 

&RPPHUFLDODJHQWV are those agents not provided under an IND but obtained instead 
from a commercial source. The NCI, rather than a commercial distributor, may on some 
occasions distribute commercial agents for a trial.
When a study includes both investigational and commercial agents, the following rules 
apply.  
Concurrent administration When an investigational agent(s) is used in combination 
with a commercial agent(s), the combination is considered to be investigational and 
expedited reporting of adverse events would follow the guidelines for investigational 
agents.
Sequential administration
When a study includes an investigational agent(s) and a 
commercial agent(s) on the same study arm with sequential administration all expedited 
reporting of adverse events should follow the guidelines for the type of agent being given.  
For example, if the patient begins the study on the investigational agent(s), then all 
expedited reporting of adverse events should follow guidelines for the investigational 
agent(s).  Once the patient begins receiving the commercial agent(s) then all expedited 
reporting of adverse events should follow the guidelines for commercial agent(s).  

6WHS  Identify the type of event using the NCI Common Terminology Criteria for 
Adverse Events (CTCAE). The CTCAE provides descriptive terminology and a grading 
scale for each adverse event listed. A copy of the CTCAE can be downloaded from the 
CTEP home page (http://ctep.cancer.gov). Additionally, if assistance is needed, the NCI 
has an Index to the CTCAE that provides help for classifying and locating terms. 
6WHS 
Grade the event using the NCI CTCAE version specified in the protocol for 
reporting serious adverse events.
CLOSED EFFECTIVE 10/01/2015
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Version Date 1/19/15
6WHS  Determine if the adverse event is Expected or an Exception to Expedited 
Reporting.  ([SHFWHG events are those that have been previously identified as resulting 
from administration of the agent and are listed in one of the following:  
x
The current NCI SPEER (Specific Protocol Exceptions to Expedited Reporting) 
for treatments using agents provided under an NCI-held IND, or an equivalent 
listing for treatments using agents provided under a Non-CTEP-held IND; located 
in Section 3.0 of the protocol.
x
For treatments using commercial agents, the current CAEPR (Comprehensive 
Adverse Event and Potential Risks), ASAEL (Agent Specific Adverse Event List), 
or other list of expected toxicities located in Section 3.0 of the protocol, or the 
drug package insert.  
An adverse event is considered XQH[SHFWHG for expedited reporting purposes only, 
when either the type of event or the severity of the event is QRW listed in one of the areas 
outlined above.
6WHS  Determine whether the adverse event involved hospitalization or a prolongation 
RIKRVSLWDOL]DWLRQKRXUV
6WHS  Additionally, for commercial drugs, determine whether the adverse event is 
related to the protocol therapy. Attribution categories are as follows: Unrelated, Unlikely, 
Possible, Probable, and Definite.  Consult the appropriate table for expedited reporting 
criteria for commercial agent(s).
127(   Any event that occurs more than 30 days after the last dose of study agent and 
is attributed (possible, probable, or definite) to the study agent(s) must be reported 
according to the instructions above and as outlined in the appropriate table in Section 
16.1. 
CLOSED EFFECTIVE 10/01/2015
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Page 51
Version Date 1/19/15
18.2
6 Intake Calendar
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Institution/Affiliate _______________________ Physician _____________________________
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This is a monthly calendar on which you are to record the number of tablets/pills/capsules you 
take each day.  Be sure you have enough calendars to last until your next appointment.  If you 
develop any side effects from the tablets/pills/capsules, mark this on the calendar on the day 
you note the effect.  Bring your calendars with you each time you have an appointment.
If you have questions contact: ____________________ Telephone: _____________________
Your next appointment is: _______________________
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S1202
Page 52
Version Date 1/19/15
18.3
Guidelines for Emergency Unblinding of Coded Drug
a.
The following events MAY require emergency unblinding of Coded Drug:
x
A compelling medical need as determined by a physician, e.g., occurrence of a 
severe or life-threatening reaction, inclusive of an adverse drug reaction, which may 
have been attributable to Coded Drug, or existence of a condition where the 
knowledge of the patient's treatment assignment would directly influence or affect 
his/her immediate care;
x
ingestion of the Coded Drug by persons other than the patient or in excessive 
quantity;
x
exposure of a pregnant woman to the Coded Drug;
x
exposure of a child to the Coded Drug;
Note:  Adverse drug reactions should be reported as required per Section 16.0 of this 
protocol.
b.
Procedure for Emergency Unblinding
The procedure for unblinding the treatment assignment for a patient is as follows:
x
All unblinding must be done by the registering physician or designee.
x
Call the Washington Poison Control (WPC) collect at 206/526-2121 or at 
800/732-6985 if calling from within Washington State.  The WPC is 
accessible 24 hours per day, 365 days per year for unblinding calls.  
Informational calls should be directed to the Data Operations Center in 
Seattle during standard business hours.
x
Provide the WPC with the following information:
Study number:  6
SWOG patient number
Patient name
Coded Drug ID number and bottle number
Name and telephone number of the caller
Reason unblinding is required
x
Unblinding for ingestion of the Coded drug by a pregnant woman will not 
require the authorization of a resource physician.  (The resource physicians 
for this study are listed at the end of this section.)
x
Unblinding for ingestion of the Coded Drug by a child will not require the 
authorization of a resource physician.
x
Unblinding for ingestion of the drug either in excessive amounts or by a 
person other than the patient will be done ONLY when a compelling medical 
need exists and/or unblinding has been authorized by a resource physician.
x
Unblinding for a "compelling medical need" must be authorized by a 
physician designated as a resource physician for this protocol.
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 53
Version Date 1/19/15
Revised 9/18/13
The treating physician (or designee) would provide the WPC with the information 
needed to determine if unblinding is required for the patient.  The WPC would 
contact the resource physician, provide the required information, and obtain the 
authorization to unblind, if necessary.  Based on the decision of the resource 
physician, the WPC would call the treating physician with either the unblinded 
treatment assignment or a treatment recommendation from the resource 
physician.
If a resource physician cannot be reached by the WPC, treatment of the patient 
should proceed as if the drug ingested were an active agent.
x
Unblinding of Coded Drug for any reason must be documented on the 6
Treatment Form and the 6 Off Treatment Notice.
All unblinded participants are taken off treatment and followed per the 
requirements of the Southwest Oncology Group protocol.
Any questions regarding unblinding may be directed to one of the following 
resource physicians:
Norah Lynn Henry, M.D., Ph.D. (Medical Oncology)
University of Michigan
Comprehensive Cancer Center
1500 E. Medical Center Drive, Med Inn Building C450
Ann Arbor, MI 48109
Phone:  734/936-4991
FAX:  734/936-4940
E-mail:  norahh@med.umich.edu
Craig R. Nichols, M.D. (Medical Oncology)
Virginia Mason Medical Center
1100 Ninth Avenue, MS:  C2-HEM
Seattle, WA  98101
Phone: 206/223-6193
FAX: 206/223-6169
E-mail: craig.nichols@vmmc.org
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DEPARTMENT OF HEALTH AND HUMAN SERVICES  
Food and Drug Administration
Silver Spring  MD  20993
IND 117788 
EXEMPT IND
SWOG                                                                          
Attention: Laurence H. Baker, D.O. 
Chairman 
Operations Office 
4201 Medical Drive, Ste 250 
San Antonio, TX  78229 
Dear Dr. Baker: 
Please refer to your Investigational New Drug Application (IND) submitted under section 505(i) 
of the Federal Food, Drug, and Cosmetic Act for Duloxetine (Cymbalta). 
After reviewing the information contained in your submission, we have concluded that your 
study, protocol S1202, entitled “A Randomized Placebo-Controlled Phase III Study of 
Duloxetine for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in 
Women with Early Stage Breast Cancer” meets all of the requirements for exemption from the 
IND regulations and, therefore, an IND is not required to conduct your investigation.  In 
accordance with 21 CFR 312.2(b)(4) of the regulations, FDA will not accept your application. 
The IND regulations [21 CFR 312.2(b)] state that the clinical investigation of a drug product, 
including a biological product, that is lawfully marketed in the United States, is exempt from the 
requirements for an IND if all of the following apply: 
1. The investigation is not intended to be reported to FDA as a well-controlled study in support
of a new indication for use, nor intended to be used to support any other significant change in
the labeling for the drug.
2. The investigation is not intended to support a significant change in the advertising for a
prescription drug product.
3. The investigation does not involve a change in route of administration, dosage level, or
patient population, or other factor that significantly increases the risks (or decreases the
acceptability of risks) associated with use of the drug product.
4. The investigation is conducted in compliance with the requirements for institutional review
(21 CFR Part 56) and informed consent (21 CFR Part 50).
Reference ID: 3270713
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IND 117788 
Page 2 
5. The investigation is conducted in compliance with the requirements of 21 CFR 312.7, i.e.,
the drug may not be represented as safe or effective, nor may it be commercially distributed,
for the purposes for which it is under investigation.
In addition, 21 CFR 312.2(b)(5) exempts from the IND requirements a clinical investigation that 
involves use of a placebo if the investigation does not otherwise require submission of an IND. 
We remind you that exemption from the requirements for an IND does not in any way exempt 
you from complying with the requirements for informed consent under 21 CFR 50.20 or from 
initial and continuing Institutional Review Board review under 21 CFR Part 56.  You are also 
responsible for complying with the applicable provisions of sections 402(i) and 402(j) of the 
Public Health Service Act (PHS Act) (42 U.S.C. §§ 282(i) and (j)), which was amended by Title 
VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public Law No. 
110-85, 121 Stat. 904). 
Title VIII of FDAAA amended the PHS Act by adding new section 402(j) (42 USC § 282(j)), 
which expanded the current database known as ClinicalTrials.gov to include mandatory 
registration and reporting of results for applicable clinical trials of human drugs (including 
biological products) and devices.  Please note that, if in the future you submit an application 
under sections 505, 515, or 520(m) of the FDCA (21 USC §§ 355, 360(e), or 360(j)(m)), or 
under section 351 of the PHS Act (21 U.S.C. § 262), or you submit a report under section 510(k) 
of the FDCA (21 USC § 360(k)), the application or submission must be accompanied by a 
certification that all applicable requirements of section 402(j) of the PHS Act (42 USC § 282(j)) 
have been met.  Where available, such certification must include the appropriate National 
Clinical Trial (NCT) control numbers (42 USC § 282(j)(5)(B)).  Additional information 
regarding the certification is available at: 
http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCA
ct/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/uc
m095442.htm. Additional information regarding Title VIII of FDAAA is available at: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html. Additional information on 
registering your clinical trial(s) is available at the Protocol Registration System website 
(http://prsinfo.clinicaltrials.gov/).
For additional information about IND regulations, you can check our web site at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm
If you have any questions, call Modupe Fagbami, Regulatory Project Manager, at (301) 796-
1348.
Sincerely,
{See appended electronic signature page} 
Robert L. Justice, M.D., M.S. 
Director 
Division of Oncology Products 1 
Office of Hematology & Oncology Products 
Center for Drug Evaluation and Research
Reference ID: 3270713
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------------------------------------------------------------------------------
-
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
FRANK H CROSS
03/04/2013
Signed for:
Robert L. Justice, M.D., M.S.
Director
Division of Oncology Products 1
Office of Hematology & Oncology Products
Center for Drug Evaluation and Research
Reference ID: 3270713
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CLOSED EFFECTIVE 10/01/2015


Page 1 
Version Date 1/19/15
Informed Consent Model for S1202
*NOTES FOR LOCAL INSTITUTION INFORMED CONSENT AUTHORS: 
This model informed consent form has been reviewed by the DCTD/NCI and is the official 
consent document for this study. Local IRB changes to this document are allowed.  (Institutions 
should attempt to use sections of this document that are in bold type in their entirety.)  Editorial 
changes to these sections may be made as long as they do not change information or intent.  If 
the institutional IRB insists on making deletions or more substantive modifications to the risks or 
alternatives sections, they may be justified in writing by the investigator and approved by the 
IRB.  Under these circumstances, the revised language, justification and a copy of the IRB 
minutes must be forwarded to the SWOG Operations Office for approval before a patient may be 
registered to this study.   
Please particularly note that the questions related to banking of specimens for future study 
are in bolded type and may not be changed in any way without prior approval from the 
SWOG Operations Office.
Readability Statistics:  
Flesch Reading Ease  
62.5 (targeted above 55) 
Flesch-Kincaid Grade Level 8.5 (targeted below 8.5) 
x
Instructions and examples for informed consent authors are in [italics].
x
A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective 
research participant. 
x
The term "study doctor" has been used throughout the model because the local 
investigator for a cancer treatment trial is a physician.   If this model is used for a 
trial in which the local investigator is not a physician, another appropriate term 
should be used instead of "study doctor".  
x
The dates of protocol updates in the header and in the text of the consent is for 
reference to this model only and should not be included in the informed consent 
form given to the prospective research participant.  
x
The local informed consent must state which parties may inspect the research 
records. This includes the NCI, the drug manufacturer for investigational studies, 
any companies or grantors that are providing study support (these will be listed in 
the protocol's model informed consent form) and SWOG.
"SWOG" must be listed as one of the parties that may inspect the research records 
in all protocol consent forms for which patient registration is being credited to 
SWOG.  This includes consent forms for studies where all patients are registered 
directly through the SWOG Data Operations Center, all intergroup studies for 
which the registration is being credited to SWOG (whether the registration is 
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 2 
Version Date 1/19/15
through the SWOG Data Operations Center or directly through the other group), as 
well as consent forms for studies where patients are registered via CTSU and the 
registration is credited to SWOG.
x
When changes to the protocol require revision of the informed consent document, 
the IRB should have a system that identifies the revised consent document, in order 
to preclude continued use of the older version and to identify file copies.  An 
appropriate method to identify the current version of the consent is for the IRB to 
stamp the final copy of the consent document with the approval date.  The stamped 
consent document is then photocopied for use.  Other systems of identifying the 
current version of the consent such as adding a version or approval date are allowed 
as long as it is possible to determine during an audit that the patient signed the most 
current version of the consent form.  
*NOTES FOR LOCAL INVESTIGATORS: 
x
The goal of the informed consent process is to provide people with sufficient 
information for making informed choices.   The informed consent form provides a 
summary of the clinical study and the individual's rights as a research participant.  
It serves as a starting point for the necessary exchange of information between the 
investigator and potential research participant.  This model for the informed consent 
form is only one part of the larger process of informed consent. For more 
information about informed consent, review the "Recommendations for the 
Development of Informed Consent Documents for Cancer Clinical Trials" prepared 
by the Comprehensive Working Group on Informed Consent in Cancer Clinical 
Trials for the National Cancer Institute.  The Web site address for this document is 
http://cancer.gov/clinicaltrials/understanding/simplification-of-informed-consent-
docs/
x
A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective 
research participant.  
x
Suggestion for Local Investigators:  An NCI pamphlet explaining clinical trials is 
available for your patients.  The pamphlet is titled: "Taking Part in Cancer 
Treatment Research Studies".  This pamphlet may be ordered on the NCI Web site 
at https://cissecure.nci.nih.gov/ncipubs or call 1-800-4- CANCER (1-800-422-
6237) to request a free copy. 
x
Optional feature for Local Investigators: Reference and attach drug sheets, 
pharmaceutical information for the public, or other material on risks.  Check with 
your local IRB regarding review of additional materials. 
*These notes for authors and investigators are instructional and should not be included in the 
informed consent form given to the prospective research participant.  
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 3 
Version Date 1/19/15
S1202, "A Randomized Placebo-Controlled Phase III Study of 
Duloxetine for Treatment of Aromatase Inhibitor (AI)-Associated 
Musculoskeletal Symptoms in Women with Early Stage Breast Cancer"
This is a clinical trial, a type of research study.  Your study doctor will explain the clinical trial 
to you.  Clinical trials include only people who choose to take part. Please take your time to 
make your decision about taking part.  You may discuss your decision with your friends and 
family.  You can also discuss it with your health care team.  If you have any questions, you can 
ask your study doctor for more explanation.  
You are being asked to take part in this study because you have been identified as having a 
history of hormone receptor positive breast cancer, are post-menopausal, are being treated with 
an aromatase inhibitor, and are experiencing joint pain.
Who is doing this study?
SWOG is sponsoring this trial.  SWOG is an adult cancer clinical trials organization. SWOG is 
funded through the National Cancer Institute, and its network consists of about four thousand 
physicians at almost three hundred institutions throughout the United States.  Your study doctor 
has met all requirements to be a member of SWOG and to perform National Cancer Institute-
funded research through this Group. 
Why is this study being done?
The purpose of this study is to assess the effects, good and/or bad, of the medication 
duloxetine compared to placebo (contains no active ingredient) on your joint pain that is 
associated with taking aromatase inhibitors.  Duloxetine is a drug usually prescribed to 
treat depression or anxiety, pain caused by nerve damage or fibromyalgia (a painful 
muscle/bone/nerve disorder) and a muscle and bone pain from a type of arthritis.  
Researchers on this study want to see if the pain relieving effects of the drug work for your 
type of pain.
How many people will take part in the study?
About 294 people will take part in this study.  
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 4 
Version Date 1/19/15
What will happen if I take part in this research study?  
Before you begin the study …  
You will need to have the following exams, tests or procedures to find out if you can be in the 
study.  These exams, tests or procedures are part of regular cancer care and may be done even if 
you do not join the study.  If you have had some of them recently, they may not need to be 
repeated.  This will be up to your study doctor. 
x
Medical history and physical exam 
x
Blood work to check your liver and kidney function 
x
Blood work to check your menopausal status (if necessary). 
You will also complete a questionnaire to collect information about joint pain that you are 
currently having.  This is not part of routine cancer care. 
During the study …  
If the exams, tests and procedures show that you can be in the study, and you choose to take part, 
then you will need the following procedures.   
x
Blood sample – Blood (about 3 teaspoons) will be taken before starting the study 
drug. The blood sample is not part of usual medical care. The blood sample will 
be submitted for specific biomarker and DNA (genetic) studies. (A biomarker is a 
biological molecule found in blood, other body fluids, or tissues that is a sign of 
normal or abnormal process, or of a condition or disease.) You and your study 
doctor will not know the results of these tests.   
x
Also, you will be asked if remaining blood from the sample can be kept for future 
research purposes. Please see separate questions at the end of this document.  
x
Questionnaires – You will complete four  questionnaires (which will take about 
20-25 minutes to complete) at the beginning of the study to collect information 
about how you are feeling physically during your treatment and how you are 
performing your daily activities. You will be asked to respond to questions 
regarding aromatase inhibitors and pain medications. You will also be asked 
questions about other symptoms you may be having, including hot flashes, sleep 
difficulties, and mood changes. If any questions make you feel uncomfortable, 
you may skip those questions and not give an answer. We will do our best to 
make sure that your personal information will be kept private.  This is not part of 
regular cancer care, but is being done as part of this research study. 
You will be "randomized" into one of the study groups described below. Randomization means 
that you are put into a group by chance, like a flip of a coin. A computer program will place you 
in one of the study groups.  Neither you nor your doctor can choose the group you will be in.  
You will have an equal chance of being placed in either group. 
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 5 
Version Date 1/19/15
You will receive duloxetine (the study drug) or you will receive placebo (which contains 
no drug). Neither you nor your doctor will know which medication you are receiving. 
During the first week, you will take 1 capsule each day. Starting the second week, you 
will take 2 capsules each day for a total of 11 weeks (77 days). For the last week, you 
will take 1 capsule each day. 
You will be supplied with study drug when you start the study and at 12 weeks.
Your doctor will give you a pill diary to keep track of your medication.  You will record 
your medication intake and your doctor or nurse will review it every month.
At the 2 Week Visit…
The medical team or staff will record:
x
Side effects you may be having 
x
Pain treatments you are receiving
x
Aromatase inhibitor use 
x
Questionnaires – You will complete five questionnaires (which will take about 
20-25 minutes to complete) at this appointment to collect information about 
how you are feeling physically during your treatment and how you are 
performing your daily activities. You will be asked to rate joint pain, and will 
be asked to respond to questions regarding aromatase inhibitors and pain 
medications. If any questions make you feel uncomfortable, you may skip those 
questions and not give an answer. We will do our best to make sure that your 
personal information will be kept private. 
At the 6 Week and 12Week Visits… 
The medical team or staff will record:
x
Side effects you may be having 
x
Pain treatments you are receiving
x
Aromatase inhibitor use 
x
Number of pills remaining in your container 
x
Questionnaires – You will complete six questionnaires (which will take about 20-25 
minutes to complete) at each of these appointments to collect information about how you 
are feeling physically during your treatment and how you are performing your daily 
activities. You will be asked to rate joint pain, and will be asked to respond to questions 
regarding aromatase inhibitors and pain medications. You will also be asked questions 
about other symptoms you may be having, including hot flashes, sleep difficulties, and 
mood changes. If any questions make you feel uncomfortable, you may skip those 
questions and not give an answer. We will do our best to make sure that your personal 
information will be kept private.
CLOSED EFFECTIVE 10/01/2015
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S1202
Page 6 
Version Date 1/19/15
During the Week 12 visit, blood (about 2 teaspoons) will be drawn. After the treatment part of 
the study is finished the blood will be used to test for biomarkers and the results of these tests 
will not be part of your medical record. 
You will be asked to take 1 capsule of study drug each day for 7 more days (until the end of 
Week 13).
At the 14 Week Visit…
The medical team or staff will contact you by telephone to ask about side effects you may be 
having. 
At the 24 Week Visit…
The medical team or staff will record:
x
Pain treatments you are receiving
x
Aromatase inhibitor use 
x
Questionnaires – You will complete five questionnaires (which will take about 20-25 
minutes to complete) at this appointment to collect information about how you are feeling 
physically and how you are performing your daily activities. You will be asked to rate 
joint pain, and you will be asked to respond to questions regarding aromatase inhibitors 
and pain medications. You will also be asked questions about other symptoms you may 
be having, including hot flashes, sleep difficulties, and mood changes. If any questions 
make you feel uncomfortable, you may skip those questions and not give an answer. We 
will do our best to make sure your personal information will be kept private. 
How long will I be in the study?
You will be asked to take duloxetine or placebo for a total of 13 weeks. After you are finished 
taking the study drugs, the study doctor will ask you to visit the office at 24 weeks for a final 
follow-up visit.
Can I stop being in the study?
Yes.  You can decide to stop at any time.  Tell the study doctor if you are thinking about 
stopping or decide to stop since suddenly stopping the study medication can cause side effects.  
He or she will tell you how to stop safely.  It is important that all patients on the study 
medication taper off slowly according to your doctor’s instructions to prevent serious side 
effects.
CLOSED EFFECTIVE 10/01/2015
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Revised 1/23/14
S1202
Page 7 
Version Date 1/19/15
It is important to tell the study doctor if you are thinking about stopping so any risks from the 
study drugs can be evaluated by your doctor.  Another reason to tell your doctor that you are 
thinking about stopping is to discuss what follow-up care and testing could be most helpful for 
you.
The study doctor may stop you from taking part in this study at any time if he/she believes it is in 
your best interest, if you do not follow the study rules, or if the study is stopped. 
What side effects or risks can I expect from being in the study? 
You may have side effects while on the study.  Everyone taking part in the study will be 
watched carefully for any side effects.  However, doctors don’t know all the side effects that 
may happen.  Side effects may be mild or very serious. Your health care team may give you 
medicines to help lessen side effects. Many side effects go away soon after you stop taking 
the study drugs. In some cases, side effects can be serious, long lasting, or may never go 
away.  
You should talk to your study doctor about any side effects that you have while taking part 
in the study.   
Risks and side effects related to duloxetine include those which are:
Likely (occurring in more than 10% of patients) (1/23/14)
x
Nausea (updated 1/23/14)
x
Headache
x
Dry mouth
x
Fatigue and tiredness
x
Difficulty sleeping
x
Moved to Less Likely 1/23/14
x
Moved to Less Likely 1/23/14
x
Moved to Less Likely 1/23/14
Less Likely(occurring in 1-10% of patients) (1/23/14)
x
Dizziness (moved from Likely 1/23/14)
x
Decreased appetite (moved from Likely 1/23/14)
x
Increased sweating (moved from Likely 1/23/14)
x
Vomiting, constipation, diarrhea (moved from Likely 1/23/14)
x
Palpitations 
x
Lightheadedness leading to loss of consciousness
x
Increased blood pressure
x
Blurry vision 
x
Abdominal pain
x
Weight loss or gain 
CLOSED EFFECTIVE 10/01/2015
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Revised 1/23/14
S1202
Revised 4/29/14
Page 8 
Version Date 1/19/15
x
Tremor
x
Anxiety
x
Sexual problems
x
Abnormal dreams
x
Yawning
x
Hot flashes
x
Fever
x
Muscle cramps
x
Numbness or tingling of fingers or toes
x
Cough 
x
Rash
x
Itching
x
Low blood sodium level
x
Difficulty urinating
Rare but serious (occurring in less than 1% of patients) (1/23/14) 
x
Suicidal thoughts or behaviors
x
Liver failure
x
Bleeding
x
Serotonin syndrome (a potentially life-threatening drug reaction caused by 
too much serotonin activity in the body; it may include agitation, 
hallucinations, coma, other changes in mental status, coordination 
problems, muscle twitching, racing heartbeat, high or low blood pressure, 
sweating, fever, nausea, vomiting, diarrhea, muscle rigidity, dizziness, 
flushing, tremor, and seizures).
x
Stevens-Johnson syndrome (severe rash that can occur in the mouth and 
on the skin and can be associated with fever; this may include skin 
sloughing-damage to the outer layer of skin causing it to separate from the 
rest of the skin).  You should contact your doctor if skin rash occurs.
After you start taking the study medication, if you have any thoughts about suicide you 
should contact the study doctor or your oncologist immediately.  Your risk of suicide will 
be monitored during the study.
You must not take MAO-Inhibitors, heparin, or warfarin while on this study. Please 
discuss with your study doctor if you are taking any of these medications or if you are given 
a prescription for them while you are on the study. You should also discuss with your 
doctor if you take aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) as the use of 
these drugs with the study drug could increase your risk of bleeding. (4/29/14) 
The researchers will try to minimize the risk of nausea by gradually increasing the dose of 
duloxetine when you first start taking the medication, and by gradually decreasing the dose 
of duloxetine when you stop taking the medication. Most of these side effects are expected 
to go away when you stop taking the drug. 
CLOSED EFFECTIVE 10/01/2015
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Revised 9/18/13
S1202
Revised 1/19/15
Page 9 
Version Date 1/19/15
Blood draws: The risks of drawing blood are minimal, but include discomfort, bruising, 
fainting or lightheadedness, and, rarely, infection and significant bleeding. To minimize the 
risks and discomfort, only trained personnel will collect blood from you during this study.
For more information about risks and side effects, ask your study doctor. 
Are there benefits to taking part in the study?
Taking part in this study may or may not make your health better.  We hope that the information 
from this study will help doctors learn whether duloxetine reduces joint pain in patients receiving 
aromatase inhibitors. This information could help future patients taking aromatase inhibitors.
What other choices do I have if I do not take part in this study?
Your other choices may include:
x
Getting treatment or care for your joint pain without being in a study 
x
Taking part in another study 
x
Getting no treatment
Talk to your doctor about your choices before you decide if you will take part in this study. 
Will my medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be 
given out if required by law.  If information from this study is published or presented at scientific 
meetings, your name and other personal information will not be used.  
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
x
[List relevant organizations like study sponsor(s), local IRB, etc.] 
x
The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), involved in keeping research safe for people 
x
The Cancer Trials Support Unit (CTSU), a research group sponsored by the National 
Cancer Institute (NCI) to provide greater access to clinical trials. (added 9/18/13)
x
SWOG
x
Alliance, ECOG-ACRIN, NRG (added 1/19/15)
x
Eli Lilly & Company, which is providing the study medication 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This Web 
site will not include information that can identify you.  At most, the Web site will include a 
summary of study results.  You can search this Web site at any time.
CLOSED EFFECTIVE 10/01/2015
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Revised 1/19/15
S1202
Page 10
Version Date 1/19/15
[Note to Local Investigators: The NCI has recommended that HIPAA regulations be addressed 
by the local institution.  The regulations may or may not be included in the informed consent 
form depending on local institutional policy.] 
What are the costs of taking part in this study?
You and/or your health plan/ insurance company will need to pay for some or all of the costs 
associated with this study (except for the research studies done on your blood as discussed 
below).  Some health plans will not pay these costs for people taking part in studies.  Check with 
your health plan or insurance company to find out what they will pay for.  Taking part in this 
study may or may not cost your insurance company more than the cost of getting regular care. 
Eli Lilly will supply the duloxetine or placebo at no charge while you take part in this study.   
Even though it probably won’t happen, it is possible that the manufacturer may not continue to 
provide the duloxetine and placebo to SWOG for some reason.  If this would occur, other 
possible options are: 
x
You might be able to get the study drug from the manufacturer or your pharmacy 
but you or your insurance company may have to pay for it. 
x
If there is no study drug available at all, no one will be able to get more and the 
study would close. 
If a problem with getting the study drug occurs, your study doctor will talk to you about these 
options. 
You will not be paid for taking part in this study. 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at 
http://m.cancer.gov/topics/clinicaltrials/learningabout/payingfor/howinsurance-companies-
decide. (updated 1/19/15) You can print a copy of the "Clinical Trials and Insurance Coverage" 
information from this Web site.
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy. 
What happens if I am injured because I took part in this study?
It is important that you tell your study doctor, __________________ [investigator’s name(s)], if 
you feel that you have been injured because of taking part in this study.  You can tell the doctor 
in person or call him/her at __________________ [telephone number].
CLOSED EFFECTIVE 10/01/2015
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Revised 4/29/14
S1202
Page 11
Version Date 1/19/15
You will get medical treatment if you are injured as a result of taking part in this study.  You 
and/or your health plan will be charged for this treatment.  The study will not pay for medical 
treatment.  
What are my rights if I take part in this study?
Taking part in this study is your choice.  You may choose either to take part or not to take part in 
the study.  If you decide to take part in this study, you may leave the study at any time.   No 
matter what decision you make, there will be no penalty to you and you will not lose any of your 
regular benefits.  Leaving the study will not affect your medical care.  You can still get your 
medical care from our institution.   
A Data Safety and Monitoring Board, an independent group of experts, will be reviewing the 
data from this research throughout the study. We will tell you about important new information 
from this or other studies that may affect your health, welfare, or willingness to stay in this study. 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form.   
Who can answer my questions about the study?
You can talk to your study doctor about any questions or concerns you have about this study.  
Contact your study doctor __________________ [name(s)] at __________________ [telephone 
number].
For questions about your rights while taking part in this study, call the 
________________________ [name of center] Institutional Review Board (a group of people 
who review the research to protect your rights) at __________________ (telephone number).  
[Note to Local Investigator: Contact information for patient representatives or other individuals 
in a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can be listed here.]    
(deleted 4/29/14) 
Please note:  This section of the informed consent form is about additional research 
studies that are being done with people who are taking part in the main study.  You 
may take part in these additional studies if you want to.  You can still be a part of 
the main study even if you say 'no' to taking part in any of these additional studies.
CLOSED EFFECTIVE 10/01/2015
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S1202
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You can say "yes" or "no" to each of the following studies.  Please mark your 
choice for each study.  
Future Contact
I agree to allow my study doctor, or someone approved by my study doctor, to 
contact me regarding future research involving my participation in this study. 
Yes
No
Consent Form for Use of Specimens for Research
About Using Specimens for Research 
You are going to have blood drawn for biomarker and DNA (genetic) testing in this study. The 
results of these tests will not be given to you or your doctor and will not be part of your medical 
record.
We would like to keep some of the blood that is left over for future research. If you agree, this 
blood will be kept and may be used in research to learn more about cancer and other diseases. 
Please read the information sheet called "How are Specimens Used for Research" to learn more 
about specimen research. 
The research that may be done with your specimens is not designed specifically to help you. It 
might help people who have cancer and other diseases in the future.  
Reports about research done with your specimens will not be given to you or your doctor. These 
reports will not be put in your health record. The research will not have an effect on your care.  
Things to Think About 
The choice to let us keep the left over specimens for future research is up to you. No matter what 
you decide to do, it will not affect your care.  
If you decide now that your specimens can be kept for research, you can change your mind at 
any time. Just contact us and let us know that you do not want us to use your specimens. Then 
any specimens that remain will no longer be used for research.  
In the future, people who do research may need to know more about your health. While SWOG
may give them reports about your health, it will not give them your name, address, phone 
number, or any other information that will let the researchers know who you are.  
Sometimes specimens are used for genetic research (about diseases that are passed on in 
families). Even if your specimens are used for this kind of research, the results will not be put in 
your health records.  
If your confidential genetic information is discovered, you may suffer from genetic 
discrimination. Genetic discrimination occurs if people are treated unfairly because of 
differences in their genes that increase their chances of getting a certain disease. In the past, this 
could have resulted in the loss of health insurance or employment. Because of this, The Genetic 
CLOSED EFFECTIVE 10/01/2015
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S1202
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Information Nondiscrimination Act of 2008, also referred to as GINA, was passed by Congress 
to protect Americans from such discrimination. The new law prevents discrimination from health 
insurers and employers. This act was signed into federal law on May 21, 2008, and went into 
effect May 2009. This law does not cover life insurance, disability insurance and long-term care 
insurance.
While this study has safeguards in place to protect your confidential genetic information and to 
make it extremely unlikely that your identity would be connected with any special studies that 
are performed on your blood, it is possible that this information could be discovered by someone 
who is unauthorized to have access to it. 
Your specimens will be used only for research and will not be sold. The research done with your 
specimens may help to develop new products in the future.  
Benefits  
 
The benefits of research using specimens include learning more about what causes cancer and 
other diseases, how to prevent them, and how to treat them.  
Risks 
The greatest risk to you is the release of information from your health records. We will do our best to 
make sure that your personal information will be kept private.  The chance that this information will be 
given to someone else is very small.  
Making Your Choice 
Please read each sentence below and think about your choice. After reading each sentence, circle 
"Yes" or "No."  If you have any questions, please talk to your doctor or nurse, or call our 
research review board at IRB's phone number.  
No matter what you decide to do, it will not affect your care. 
1.
My specimens may be kept for use in research to learn about, prevent, treat or cure 
cancer. 
Yes
No
2.
My specimens may be kept for use in research about other health problems (for 
example: diabetes, Alzheimer's disease, or heart disease). 
Yes
No
3.
Someone may contact me in the future to ask me to allow other uses of my 
specimens.
Yes
No
CLOSED EFFECTIVE 10/01/2015
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Revised 4/29/14
S1202
Revised 1/19/15
Page 14
Version Date 1/19/15
If you decide to withdraw your specimens from a SWOG Specimen Repository in the 
future, a written withdrawal of consent should be submitted through your study doctor to 
the SWOG Operations Office.  Please designate in the written withdrawal whether you 
would prefer to have the specimens destroyed or returned to the study doctor.
Where can I get more information?
You may call the National Cancer Institute's Cancer Information Service at: 
1-800-4-CANCER (1-800-422-6237)  
You may also visit the NCI Web site at http://cancer.gov/ 
x
For NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials/
x
For NCI’s general information about cancer, go to http://cancer.gov/cancerinfo/ 
You will get a copy of this form.  If you want more information about this study, ask your study 
doctor.
Signature 
I have been given a copy of all _____ [insert total of number of pages] pages of this form.  I 
have read it or it has been read to me.  I understand the information and have had my questions 
answered.  I agree to take part in this study. 
Participant ________________________________ 
(deleted 1/19/15) 
Date _____________________________________
CLOSED EFFECTIVE 10/01/2015
ncer.gov/clin
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A specimen may be from a blood sample or from bone marrow, skin, toenails or other body materials.  
People who are trained to handle specimens and protect donors' rights make sure that the highest 
standards of quality control are followed by SWOG.  Your doctor does not work for SWOG, but has 
agreed to help collect specimens from many patients.  Many doctors across the country are helping in the 
same way.  
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Research with specimens can help to find out more about what causes cancer, how to prevent it, how to 
treat it, and how to cure it.  Research using specimens can also answer other health questions.  Some of 
these include finding the causes of diabetes and heart disease, or finding genetic links to Alzheimer's.
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Many different kinds of studies use specimens.  Some researchers may develop new tests to find 
diseases.  Others may develop new ways to treat or even cure diseases.  In the future, some of the 
research may help to develop new products, such as tests and drugs.  Some research looks at diseases 
that are passed on in families (called genetic research).  Research done with your specimen may look for 
genetic causes and signs of disease.
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Researchers from universities, hospitals, and other health organizations conduct research using 
specimens.  They contact SWOG and request samples for their studies.  SWOG reviews the way that 
these studies will be done, and decides if any of the samples can be used. SWOG gets the specimen and 
information about you from your hospital, and sends the specimen samples and some information about 
you to the researcher.  SWOG will not send your name, address, phone number, social security number 
or any other identifying information to the researcher.
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You will not receive the results of research done with your specimen.  This is because research can take 
a long time and must use specimen samples from many people before results are known.  Results from 
research using your specimen may not be ready for many years and will not affect your care right now, 
but they may be helpful to people like you in the future.
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In order to do research with your specimen, researchers may need to know some things about you.  (For 
example:  Are you male or female?  What is your race or ethnic group? How old are you?  Have you ever 
smoked?)  This helps researchers answer questions about diseases.  The information that will be given to 
the researcher may include your age, sex, race, diagnosis, treatments and family history.  This 
information is collected by your hospital from your health record and sent to SWOG.  If more information 
is needed, SWOG will send it to the researcher.
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No.  Your name, address, phone number and anything else that could identify you will be removed before 
they go to the researcher.  The researcher will not know who you are.
CLOSED EFFECTIVE 10/01/2015
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Sometimes, health records have been used against patients and their families.  For example, insurance 
companies may deny a patient insurance or employers may not hire someone with a certain illness (such 
as AIDS or cancer).  The results of genetic research may not apply only to you, but to your family 
members too.  For disease caused by gene changes, the information in one person's health record could 
be used against family members.
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SWOG is in charge of making sure that information about you is kept private.  SWOG will take careful 
steps to prevent misuse of records.  Your name, address, phone number and any other identifying 
information will be taken off anything associated with your specimen before it is given to the researcher.  
This would make it very difficult for any research results to be linked to you or your family.  Also, people 
outside the research process will not have access to results about any one person which will help to 
protect your privacy.
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