Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain

NCT01912612 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: UMCC 2013.044HUM00075181HCI94979
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Pain

Keywords

Breast cancer; Pain sensitivity

Outcome Measures

Primary Outcomes (1)

• Change in Patient-reported Worst Pain Between Baseline and 5 Weeks of Treatment With Duloxetine

  Worst pain will be assessed at baseline and 5 weeks for each individual patient using the Brief Pain Inventory. * Baseline: Mean worst pain for all individual patients in arm 1 (intervention) and arm 2 (control) * 5 weeks: Mean worst pain for all individual patients in arm 1 (intervention) * Range of pain score 0-10 (0=no pain; 10=worst pain)

  5 weeks

Secondary Outcomes (18)

• Change in Patient-reported Average Pain Between Baseline and 5 Weeks of Treatment With Duloxetine

  5 weeks

• Change in Pain Interference Between Baseline and 5 Weeks of Treatment With Duloxetine

  5 weeks

• Change in Number of Sites of Pain Between Baseline and 5 Weeks of Treatment With Duloxetine

  5 weeks

• Change in Fibromyalgia Symptom Severity Score Between Baseline and 5 Weeks of Treatment With Duloxetine

  5 weeks

• Change in PainDETECT Score Between Baseline and 5 Weeks of Treatment With Duloxetine

  5 weeks

Study Arms (2)

Arm 1 (Patients with pain, duloxetine)

EXPERIMENTAL

Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks.

Drug: Duloxetine

Arm 2 (Patients without pain -- control)

NO INTERVENTION

Patient reported pain and symptoms assessment for comparison at baseline.

Interventions

Duloxetine DRUG

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.

Also known as: Cymbalta

Arm 1 (Patients with pain, duloxetine)

Eligibility Criteria

• Age: 25 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients at least 25 years of age
• 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.
• Pain that developed or worsened since breast cancer diagnosis and is not due to identifiable traumatic event or fracture
• Patient-reported worst pain score between 5 and 10 (inclusive) on a 0-10 scale (assessed verbally)
• Female patients must be at least 1 year postmenopausal or surgically sterile; or must agree to use a medically acceptable form of contraception
• Willing to withdraw from selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) prior to treatment initiation
• 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
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

You may not qualify if:

• Prior use of duloxetine or milnacipran.
• 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)
• 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.
• Thumbnail abnormalities on either hand (such as due to chemotherapy or trauma, or artificial nails) that are likely to alter pain perception during testing
• Peripheral sensory neuropathy at the thumbs bilaterally that interferes with function and/or activities of daily living
• Significant risk of suicide based on the Investigator's judgment
• History or behavior that would, in the Investigator's judgment, prohibit compliance for the duration of the study.
• History of alcohol or other substance abuse or dependence within the year prior to registration
• Known chronic liver disease, end stage renal disease, or creatinine clearance \<30 mL/min as defined by Cockcroft-Gault equation
• Uncontrolled narrow-angle glaucoma.
• Clinically significant coagulation disorder
• History of seizure disorder
• Pregnant or breast-feeding. Urine pregnancy test will be assessed at the baseline visit in women of child-bearing potential with chronic pain.
• Unable to take oral medications or any medical condition that would interfere with the absorption of study medication capsules.
• 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).

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• American Cancer Society, Inc.: collaborator

Study Sites (2)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48103, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Pain; Breast Neoplasms

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Lynn Henry, MD, PhD
• Organization: University of Michigan Rogel Cancer Center

norahh@med.umich.edu

734-936-9868

Study Officials

• Lynn Henry, MD, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 29, 2013
• First Posted: July 31, 2013
• Study Start: October 30, 2013
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: August 6, 2020
• Results First Posted: August 6, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)