A Randomized Placebo-Controlled Phase III Study of Duloxetine for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in Women With Early Stage Breast Cancer
A Randomized Placebo-Controlled Phase III Study of Duloxetine for Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptoms in Women With Early Stage Breast Cancer
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.
OBJECTIVES:
Primary
Secondary
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.
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.
DISEASE CHARACTERISTICS:
PATIENT CHARACTERISTICS:
Patients must be post-menopausal, as defined by at least one of the following:
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:
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
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
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