Mechanistic Study of Duloxetine in Breast Cancer Patients With Chronic Pain

NCT ID: NCT01912612

Last Updated: 2020-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-30
• Study Completion Date: 2019-06-28

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.

Detailed Description

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.

Data from a randomized, placebo-controlled clinical trial of duloxetine demonstrated that it is effective in management of both aromatase inhibitor-associated musculoskeletal pain and chemotherapy-induced neuropathic pain. In this mechanistic study, we investigated 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. The original protocol was designed as a randomized, placebo-controlled cross-over trial, with planned enrollment of 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. However because of challenges with logistics of the protocol and pain testing, the trial was redesigned after only 7 patients with pain were enrolled. The new design was a single arm trial, and all patients with pain were treated with duloxetine (no placebo); there was still a non-treatment comparator arm of patients without pain. Patients were enrolled first at the University of Michigan and then the University of Utah. A total of 39 patients with pain and 43 controls without pain were enrolled before the trial closed to enrollment. All subjects underwent assessment of pain sensitivity and completed questionnaires. Subjects with pain were treated with duloxetine for a total of 7 weeks, with pain sensitivity assessments before treatment and after 4 weeks of full-dose treatment. The data from the control patients (who did not receive any study medication) are being compared to those from the patients with pain to understand more about the differences between patients who do and do not experience treatment-related pain, and to interpret the post-intervention patient-reported and pain assessment results.

Conditions

Pain

Study Design

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

Study Groups

Arm 1 (Patients with pain, duloxetine)

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

Group Type: EXPERIMENTAL

Duloxetine

Intervention Type: 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.

Arm 2 (Patients without pain -- control)

Patient reported pain and symptoms assessment for comparison at baseline.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Duloxetine

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 Type: DRUG

Other Intervention Names

Cymbalta

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)

• Minimum Eligible Age: 25 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

American Cancer Society, Inc.

OTHER

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lynn Henry, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HUM00075181

Identifier Type: OTHER

Identifier Source: secondary_id

HCI94979

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2013.044

Identifier Type: -

Identifier Source: org_study_id