Clinical trial NCT01028352: Study to Assess Effect of 8 Wks of Duloxetine Therapy on Breast Cancer Patients With Aromatase-Inhibitor Associated Pain
Official title: UMCC 2008.62: Prospective Pilot Study Evaluating the Use of Duloxetine for Treatment of Aromatase Inhibitor-associated Musculoskeletal Symptoms in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2009-12-09
Enrollment: 35
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Patients Who Experience 30% Reduction in Average Pain Score From Baseline to 8 Weeks Due to Duloxetine Therapy.
timeFrame: 8 weeks
Secondary outcomes:
measure: Decrease in Average Pain With 8 Weeks of Duloxetine Therapy. (Sustained)
timeFrame: Baseline, 2, 4 , 6 and 8 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan
name: Norah L Henry, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.