S1202: Duloxetine Hydrochloride for Muscle/Joint Pain in Early-Stage Breast Cancer Receiving Hormone Therapy
Condition: Breast Cancer; Musculoskeletal Complications; Pain
MeSH terms: Breast Neoplasms
Intervention: duloxetine hydrochloride; placebo
Intervention description: Given PO; Given PO
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 299.0
Sex: Female
Maximum age: 120 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Patients must be women with histologically confirmed estrogen receptor (ER)- and/or
             progesterone receptor (PgR)-positive invasive carcinoma of the breast 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

          -  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

        PATIENT CHARACTERISTICS:

          -  Patients must be post-menopausal, as defined by at least one of the following:

               -  At least 12 months since the last menstrual period

               -  Prior bilateral oophorectomy

               -  Previous hysterectomy with one or both ovaries left in place (or previous
                  hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND
                  follicle-stimulating hormone (FSH) values consistent with the institutional
                  normal values for the post menopausal state; if patient is under the age of 55,
                  FSH levels must be obtained within 28 days prior to registration OR

               -  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.

          -  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

          -  Creatinine clearance > 30 mL/min

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both within 3 x
             upper limit of normal

          -  Total bilirubin within the upper limit of normal

          -  Patients must be able to complete study questionnaires in English or Spanish

          -  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 must be willing to submit blood samples for correlative studies; baseline
             samples must be obtained prior to beginning protocol treatment

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  If patients were treated with chemotherapy and/or radiation therapy, these treatments
             must be completed at least 28 days prior to study registration

          -  Concurrent bisphosphonate and trastuzumab therapies are allowed

          -  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

          -  Patients must currently be taking one of the following aromatase inhibitor (AI) doses
             for at least 21 days, but no longer than 12 months, prior to registration and plans to
             continue for at least an additional 180 days after registration

               -  Anastrozole (Arimidex®) 1 mg daily

               -  Letrozole (Femara®) 2.5 mg daily

               -  Exemestane (Aromasin®) 25 mg daily

          -  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 monoamine oxidase (MAO)-inhibitor within 14
             days prior to registration; or current use of anticoagulation medication (e.g.,
             heparin, warfarin)

          -  Patients must not require selective serotonin reuptake inhibitors (SSRIs), serotonin
             and norepinephirine reuptake inhibitors (SNRIs), 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; patients must not have
             taken duloxetine or milnacipran within 90 days prior to registration

          -  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