Duloxetine Hydrochloride in Treating Muscle, Bone, and Joint Pain in Patients With Early-Stage Breast Cancer Receiving Hormone Therapy

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, Supportive careNot specifiedS1202
NCI-2012-01960, CDR0000730691, SWOG-S1202, NCT01598298

Trial Description



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. 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.

Further Study Information


I. To assess whether daily duloxetine (duloxetine hydrochloride) 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).


I. To assess whether daily duloxetine decreases worst joint pain in women with AIMSS, as measured at 12 weeks by the modified BPI-SF.

II. To assess whether daily duloxetine decreases pain interference in women with AIMSS, as measured at 12 weeks by the modified BPI-SF.


I. 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.

II. 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).

III. To investigate whether daily duloxetine improves functional quality of life as measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES).

IV. 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.

V. To investigate whether daily duloxetine improves/decreases analgesic use.

VI. To investigate whether daily duloxetine improves/increases adherence to, and reduces the discontinuation rate for, aromatase inhibitor (AI) therapy.

VII. 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).

VIII. To explore the relationship between inherited variants in genes responsible for duloxetine metabolism and activity (catechol-O-methyltransferase [COMT], 5-hydroxytryptamine (serotonin) receptor 3A, ionotropic [HTR3A], solute carrier family 6 (neurotransmitter transporter), member 2 [SLC6A2], solute carrier family 6 (neurotransmitter transporter), member 4 [SLC6A4], cytochrome P450, family 1, subfamily A, polypeptide 2 [CYP1A2], cytochrome P450, family 2, subfamily D, polypeptide 6 [CYP2D6]) and aromatase (cytochrome P450, family 19, subfamily A, polypeptide 1 [CYP19A1]) and change in pain with 12 weeks of treatment.

IX. To explore the impact of treatment on serum inflammatory cytokine levels with 12 weeks of treatment at baseline and 12 weeks.

X. To bank blood samples for future correlative analyses.

OUTLINE: 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.

Eligibility Criteria

Inclusion Criteria:

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)

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

Patients must be post-menopausal, as defined by at least one of the following:

>= 12 months since the last menstrual period OR

Prior bilateral oophorectomy OR

Previous hysterectomy with one or both ovaries left in place (or previous hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND (unless >= 60 years of age) follicle-stimulating hormone (FSH) values consistent with the institutional normal values for the postmenopausal state

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:

Anastrozole (Arimidex) 1 mg daily

Letrozole (Femara) 2.5 mg daily

Exemestane (Aromasin) 25 mg daily

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

Patients must have completed the S1202 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

Patients must have Zubrod performance status of 0-2

Patients must have no known allergy or hypersensitivity to duloxetine or any of the inactive ingredients in the matching placebo

Patients must not have any contraindicated concurrent illnesses listed on the duloxetine package insert including:

Current primary psychiatric diagnosis (schizophrenia, psychosis) or suicidal ideation, history of bipolar disorder, or seizure disorder

History of alcohol or other substance abuse or dependence within 365 days prior to registration

Chronic liver disease

End-stage renal disease

Uncontrolled narrow-angle glaucoma

Clinically significant coagulation disorder

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

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

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both within 3 x upper limit of normal based on institutional values

Total bilirubin within the upper limit of normal based on institutional values

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); patients must not have previously taken the serotonin norepinephrine reuptake inhibitors (SNRI) duloxetine or milnacipran; prior venlafaxine is allowed as long as it was not taken concurrently with AI therapy and was not taken for treatment of pain (e.g., prior treatment for hot flashes is permitted)

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

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

Patients must be able to complete study questionnaires in English

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), or cancer involving the bone; patients with

osteoarthritis are eligible

Patients must be willing to submit blood samples for correlative studies; baseline samples must be obtained prior to beginning protocol treatment

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

As a part of the Oncology Patient Enrollment Network (OPEN) registration process 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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators


  • National Cancer Institute
Norah Lynn Henry, Principal Investigator

Trial Sites



Colorado Cancer Research Program CCOP

Keren Sturtz
Ph: 888-785-6789

Keren Sturtz
Principal Investigator


Sacred Heart Medical Oncology Group - Davis Highway

James F. Watkins
Ph: 850-416-4611

James F. Watkins
Principal Investigator


Heartland Cancer Research NCORP

Norah Lynn Henry
Ph: 734-936-4991
Email: norahh@med.umich.edu

Norah Lynn Henry
Principal Investigator


Illinois CancerCare-Galesburg Cottage Plaza Office

Nguyet Anh Le-Lindqwister
Ph: 800-793-2262

Nguyet Anh Le-Lindqwister
Principal Investigator

South Bend

Northern Indiana Cancer Research Consortium CCOP

Robin T. Zon
Ph: 574-234-5123

Robin T. Zon
Principal Investigator

Des Moines

Iowa-Wide Oncology Research Coalition NCORP

Robert J. Behrens
Ph: 515-282-2921

Robert J. Behrens
Principal Investigator


Montana Cancer Consortium NCORP

Benjamin T. Marchello
Ph: 800-648-6274

Benjamin T. Marchello
Principal Investigator


Missouri Valley Cancer Consortium

Gamini S. Soori
Ph: 402-398-6060

Gamini S. Soori
Principal Investigator

Las Vegas

Nevada Cancer Research Foundation CCOP

John Allan Ellerton
Ph: 702-384-0013

John Allan Ellerton
Principal Investigator

New York
New York

Columbia University Medical Center

Norah Lynn Henry
Ph: 734-936-4991
Email: norahh@med.umich.edu

Norah Lynn Henry
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01598298

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.