Study to Assess Effect of 8 Wks of Duloxetine Therapy on Breast Cancer Patients With Aromatase-Inhibitor Associated Pain

NCT ID: NCT01028352

Last Updated: 2013-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2011-10-31

Brief Summary

Many women with breast cancer who are treated with aromatase inhibitor medications develop aches and pains during treatment, and some develop numbness and tingling in their hands and feet. Some examples of aromatase inhibitor medications include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). Frequently, pain medications do not work very well to relieve the pain. Duloxetine (Cymbalta) is a medication that was originally developed to treat depression. It has also been found to relieve pain that occurs in people with diabetes, fibromyalgia, arthritis, and other painful conditions. In this study we are testing to see if duloxetine will help treat the pain that can occur in women treated with aromatase inhibitors.

Detailed Description

Aromatase inhibitor (AI) therapy is commonly used for treatment of postmenopausal women with hormone receptor-positive breast cancer. The most common toxicities are arthralgias and myalgias, which can be difficult to manage and necessitate discontinuation of therapy in up to 10% of patients. One potential interventional approach is with a pharmaceutical agent such as duloxetine, which has been shown to be effective for treatment of other types of chronic pain, including fibromyalgia and diabetic neuropathic pain.

The primary objective of this pilot study is to determine the proportion of breast cancer patients with AI-associated musculoskeletal symptoms who experience a 30% reduction in average pain score from baseline to 8 weeks due to duloxetine treatment. Participants will be treated with duloxetine for 8 weeks. Questionnaires to evaluate pain, functional status, depression, menopausal symptoms, and sleep difficulties will be administered at baseline and after 2, 4, 6, and 8 weeks of therapy. In addition, 10 milliliters blood of will be drawn from the subjects at baseline for future pharmacogenetic evaluation. If the results of this pilot study suggest that the efficacy of duloxetine therapy is greater than that expected from placebo based on historical controls, then these data will be used to design future prospective, placebo-controlled, randomized trials of treatment with duloxetine in this patient population.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Duloxetine

Group Type: OTHER

Duloxetine

Intervention Type: DRUG

Patients will be treated with open-label duloxetine:

• 30 mg daily x 7 days, then
• 60 mg daily x 3 weeks, then
• If a patient believes she has experienced a sufficient reduction in pain after 4 weeks of therapy, she will continue taking 60 mg daily for weeks 5-8
• If a patient does not believe she has experienced a sufficient reduction in pain after 4 weeks of therapy, she will have the option of increasing the dose to 60 mg twice daily for weeks 5-8.
• After completion of 8 weeks of therapy, patients who wish to discontinue therapy will taper off the drug over 1 week (50% decrease for 4 days, then additional 50% decrease for 3 days). Patients may continue therapy off-study at the discretion of their treating physician.

Interventions

Duloxetine

Patients will be treated with open-label duloxetine:

• 30 mg daily x 7 days, then
• 60 mg daily x 3 weeks, then
• If a patient believes she has experienced a sufficient reduction in pain after 4 weeks of therapy, she will continue taking 60 mg daily for weeks 5-8
• If a patient does not believe she has experienced a sufficient reduction in pain after 4 weeks of therapy, she will have the option of increasing the dose to 60 mg twice daily for weeks 5-8.
• After completion of 8 weeks of therapy, patients who wish to discontinue therapy will taper off the drug over 1 week (50% decrease for 4 days, then additional 50% decrease for 3 days). Patients may continue therapy off-study at the discretion of their treating physician.

Intervention Type: DRUG

Other Intervention Names

Cymbalta

Eligibility Criteria

Inclusion Criteria

• Female;
• Histologically proven stage 0-III invasive carcinoma of the breast that is ER and/or PR positive by immunohistochemical staining, who are receiving a standard dose of aromatase inhibitor (AI) therapy (letrozole 2.5mg once daily or exemestane 25mg once daily or anastrozole 1mg once daily). Women with oligometastatic disease may be included at the discretion of the principal investigator. Surgical resection, chemotherapy, and radiation therapy must have been completed at the time of study enrollment, with the exception of trastuzumab;
• AI therapy has been ongoing for ≥ 2 weeks and treatment is expected to continue;
• AI-associated musculoskeletal symptoms, defined as:

• Grade 1 or higher musculoskeletal pain that developed or worsened (6 or 7 on CGICS) during AI therapy or
• Grade 1 or higher sensory neuropathy that developed or worsened (6 or 7 on CGICS) during AI therapy;
• Average pain of ≥4 on the 11-point Likert scale of question #5 of the Brief Pain Inventory;
• ECOG performance status 0-2;
• Willing and able to sign an informed consent document.

Exclusion Criteria

• Known hypersensitivity to duloxetine or any of the inactive ingredients;
• New musculoskeletal pain that is due specifically to fracture or traumatic injury;
• Treatment with monoamine oxidase inhibitors (MAO-I) within 14 days of enrollment;
• Concurrent treatment with phenothiazines (including thioridazine), propafenone, flecainide, triptans, MAO-Is, SSRIs, SNRIs, or tricyclic antidepressants;
• Currently primary psychiatric diagnosis (schizophrenia, psychosis) or suicidal ideation, history of bipolar disorder, or seizure disorder;
• Chronic liver disease, end stage renal disease, or creatinine clearance < 30 mL/min as defined by the Cockroft-Gault equation;
• Uncontrolled narrow-angle glaucoma or clinically significant coagulation disorder;
• Pregnant or breast feeding;
• History of alcohol or other substance abuse or dependence within the year prior to enrollment;
• Serious or unstable medical condition that could likely lead to hospitalization during the course of the study or compromise study participation.

• Minimum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Lynn Henry

Assistant Professor of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Norah L Henry, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Countries

United States

References

Henry NL, Banerjee M, Wicha M, Van Poznak C, Smerage JB, Schott AF, Griggs JJ, Hayes DF. Pilot study of duloxetine for treatment of aromatase inhibitor-associated musculoskeletal symptoms. Cancer. 2011 Dec 15;117(24):5469-75. doi: 10.1002/cncr.26230. Epub 2011 Jun 20.

Reference Type: RESULT

PMID: 21692065 (View on PubMed)

Other Identifiers

HUM00022455

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2008.062

Identifier Type: -

Identifier Source: org_study_id