Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain
Condition: Pain
MeSH terms: Chronic Pain
Intervention: Duloxetine
Intervention description: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Trial was initially a randomized cross-over design. Soon after study initiation the trial design was amended because of poor accrual, and instead was a single arm open label trial in which all patients with pain were treated with study drug. Since so few patients had been enrolled at the time of study redesign, the only data analyzed were from the single treatment arm portion of the trial, and the non-intervention (baseline only) comparator.
Masking: None (Open Label)
Enrollment: 82.0
Sex: Female
Minimum age: 25 Years
Healthy volunteers: No
Keywords: Breast cancer; Pain sensitivity

Summary:

      Early stage breast cancer is typically treated with surgery, chemotherapy, radiation therapy,
      and/or endocrine therapy. Following treatment, 25-60% of breast cancer survivors have
      reported chronic pain, which can be difficult to manage. Duloxetine is a serotonin
      norepinephrine reuptake inhibitor that is FDA approved for treatment of depression, anxiety,
      fibromyalgia, diabetic neuropathic pain, knee arthritis, and low back pain.

      Pilot data suggest that duloxetine is effective in management of endocrine therapy-associated
      musculoskeletal pain, and a randomized placebo controlled trial of duloxetine has
      demonstrated efficacy for treatment of chemotherapy-induced neuropathic pain. In this
      mechanistic study of duloxetine, we will investigate the change in pain sensitivity with
      treatment in order to evaluate both why duloxetine is effective for management of pain for
      some patients, as well as predictors of who is likely to benefit from duloxetine. A total of
      84 women with early stage breast cancer who have chronic pain following treatment, as well as
      48 women who are pain free, will be enrolled. All subjects will undergo assessment of pain
      sensitivity and complete questionnaires. Subjects with pain will be treated with duloxetine
      for a total of 7 weeks, with pain sensitivity assessments before treatment and after 4 weeks
      of full-dose treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female patients at least 25 years of age

          2. Diagnosis of stage 0-III breast cancer within 12 years prior to enrollment. All
             indicated surgery, chemotherapy, and/or radiation therapy must have been completed at
             least 12 weeks prior to enrollment. Concomitant endocrine therapy and targeted
             therapies such as palbociclib, pertuzumab, and trastuzumab are permitted.

          3. Pain that developed or worsened since breast cancer diagnosis and is not due to
             identifiable traumatic event or fracture

          4. Patient-reported worst pain score between 5 and 10 (inclusive) on a 0-10 scale
             (assessed verbally)

          5. Female patients must be at least 1 year postmenopausal or surgically sterile; or must
             agree to use a medically acceptable form of contraception

          6. Willing to withdraw from selective serotonin reuptake inhibitors (SSRI) and tricyclic
             antidepressants (TCA) prior to treatment initiation

          7. Patients who are currently taking non-steroidal anti-inflammatory drugs (NSAIDs)
             (e.g., ibuprofen, naproxen, meloxicam, gabapentin, pregabalin) and/or opioid pain
             medications must remain on a stable dosage throughout the duration of the study

          8. Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines.

        Exclusion Criteria:

          1. Prior use of duloxetine or milnacipran.

          2. Prior or current use of venlafaxine specifically for treatment of pain (prior or
             current use for treatment of other indications, such as hot flashes, is permitted,
             although cases currently taking venlafaxine must discontinue use prior to study
             treatment initiation)

          3. Patients must not be taking any contraindicated medications listed on the duloxetine
             package insert including the following: phenothiazines, propafenone, flecainide,
             linezolid, or anticoagulation medication (e.g., heparin, warfarin, or direct oral
             anticoagulants); treatment with monoamine oxidase inhibitor within 14 days prior to
             registration.

          4. Thumbnail abnormalities on either hand (such as due to chemotherapy or trauma, or
             artificial nails) that are likely to alter pain perception during testing

          5. Peripheral sensory neuropathy at the thumbs bilaterally that interferes with function
             and/or activities of daily living

          6. Significant risk of suicide based on the Investigator's judgment

          7. History or behavior that would, in the Investigator's judgment, prohibit compliance
             for the duration of the study.

          8. History of alcohol or other substance abuse or dependence within the year prior to
             registration

          9. Known chronic liver disease, end stage renal disease, or creatinine clearance <30
             mL/min as defined by Cockcroft-Gault equation

         10. Uncontrolled narrow-angle glaucoma.

         11. Clinically significant coagulation disorder

         12. History of seizure disorder

         13. Pregnant or breast-feeding. Urine pregnancy test will be assessed at the baseline
             visit in women of child-bearing potential with chronic pain.

         14. Unable to take oral medications or any medical condition that would interfere with the
             absorption of study medication capsules.

         15. Currently taking SSRI, serotonin-norepinephrine reuptake inhibitor (SNRI), or TCA
             regimen (including Wellbutrin) for treatment of major depressive disorder or
             generalized anxiety disorder (without approval and involvement of the patient's
             treating psychiatrist to taper cases off these medications prior to study treatment).

        Controls are patients without chronic pain who otherwise meet the following eligibility
        criteria (inclusion #1, 2, 8, exclusion #1, 2, 4, 5, worst pain score 0-1, and not
        currently on medication for pain)