Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

Phase 3

Completed

Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Neurotoxicity
Pain
Peripheral Neuropathy

Interventions: Drug: duloxetine hydrochloride
Other: placebo

Registration Number: NCT00489411

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary: RATIONALE: Duloxetine may lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether duloxetine is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy.

PURPOSE: This randomized phase III trial is studying duloxetine to see how well it works compared with a placebo in treating peripheral neuropathy caused by chemotherapy in patients with cancer.

Detailed Description: OBJECTIVES:

Primary

* Determine the efficacy of duloxetine hydrochloride in cancer patients with painful chemotherapy-induced (taxane or platinum agent) peripheral neuropathy.

Secondary

* Determine the influence of this drug on peripheral neuropathy-related functional status and quality of life of these patients.

* Describe the differences in duloxetine hydrochloride efficacy when used to treat pain caused by chemotherapy-induced peripheral neuropathy based on the neurotoxic drug and class.

OUTLINE: This is a randomized, double-blind, placebo-controlled, crossover study. Patients are stratified according to prior neurotoxic agent (paclitaxel vs oxaliplatin vs other taxane agents without paclitaxel vs platinum agents \[cisplatin\] without oxaliplatin) and high risk for developing painful chemotherapy-induced peripheral neuropathy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral duloxetine hydrochloride once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive an oral placebo once or twice daily in weeks 8-13.

* Arm II: Patients receive an oral placebo once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive oral duloxetine hydrochloride once or twice daily in weeks 8-13.

Patients complete pain and quality of life questionnaires, including the BPI-SF once weekly and FACT/GOG-NTX and EORTC QLQ-C30 questionnaires, in weeks 1, 6, 8, and 13.

After completion of study treatment, patients are followed for 2 weeks.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 231

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm I/Group A (Duloxetine then Placebo)	duloxetine hydrochloride	Patients receive oral duloxetine hydrochloride once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive an oral placebo once or twice daily in weeks 8-13.
Arm I/Group A (Duloxetine then Placebo)	placebo	Patients receive oral duloxetine hydrochloride once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive an oral placebo once or twice daily in weeks 8-13.
Arm II/Group B (Placebo then Duloxetine)	duloxetine hydrochloride	Patients receive an oral placebo once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive oral duloxetine hydrochloride once or twice daily in weeks 8-13.
Arm II/Group B (Placebo then Duloxetine)	placebo	Patients receive an oral placebo once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive oral duloxetine hydrochloride once or twice daily in weeks 8-13.

Primary Outcome Measures

Name	Time	Method
Change in Average Pain From Week 1 to Week 5, as Measured by the BPI-SF Average Pain Severity Item	Day 1 of Week 1 to Day 1 of Week 6	Change in average pain from Week 1 to Week 5, measured on day 1 of Weeks 1 and 6 by the Brief Pain Inventory Short Form (BPI-SF) was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values. The BPI-SF contains 4 items assessing average, worst, least, and intermediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Average pain severity was chosen as the primary outcome based on recommendations from the Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT). Patients completed the BPI-SF when thinking only about pain from peripheral neuropathy. The Cronbach's alpha reliability for the BPI ranges between 0.77 and 0.91. The comparison of interest was the difference between the 2 treatment groups in pain change during the initial treatment period.

Secondary Outcome Measures

Name	Time	Method
Change in Pain-related Functional Interference Score From Week 1 to Week 5, as Measured by the BPI-SF Interference Score	Day 1 of Week 1 to Day 1 to Week 6	Change in pain-related functional interference score during the initial treatment period (Week 1 to Week 5), as measured by the BPI-SF interference score: Using an accepted method for accessing the influence of pain on function, 7 BPI-SF items were used to quantify the degree to which pain interfered with daily activities or function (0, does not interfere; 10 completely interferes). The 7 items were summed to obtain a total interference score, which ranged from 0 to 70, with lower scores meaning less interference. The mean change in pain-related functional interference score during the initial treatment period are reported below for each treatment arm and was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values.
Change in the Total Score of the FACT/COG-NTX From Week 1 to Week 5	Day 1 of Week 1 to Day 1 of Week 6	Patient-reported QOL was assessed using the Functional Assessment of Cancer Treatment, Gynecologic Oncology Group Neurotoxicity (FACT/GOG-Ntx) subscale on day 1 of weeks 1, 6, 8, and 13. The instrument contains 11 questions, assessing numbness, tingling, and discomfort in the hands or feet; difficulty hearing; tinnitus; joint pain or muscle cramps; weakness; or trouble walking, buttoning buttons, or feeling small shapes when placed in the hand. Items are scored from 0 to 4 (o, not at all; 4, very much) and summed (total score range, 0-44, with higher scores indicating a worse outcome). A 2- to 3-point change is defined as a clinically meaningful improvement in QOL per published recommendations specific to similar measures. The Mean Change During Initial Treatment Period in the FACT/GOG-Ntx total score are reported for each treatment arm and was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values.
Change in Average Pain From Week 8 to Week 12, as Measured by the BPI-SF Average Pain Severity Item	Day 1 of Week 8 to Day 1 of Week 13	Change in average pain from Week 8 to Week 12, measured on day 1 of Weeks 8 and 13 by the Brief Pain Inventory Short Form (BPI-SF) was calculated as value at Day 1 of Week 8 minus value at Day 1 of Week 13 to yield positive improvement values. The BPI-SF contains 4 items assessing average, worst, least, and intermediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Average pain severity was chosen as the primary outcome based on recommendations from the Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT). Patients completed the BPI-SF when thinking only about pain from peripheral neuropathy. The Cronbach's alpha reliability for the BPI ranges between 0.77 and 0.91. The comparison of interest was the difference between the 2 treatment groups in pain change during the crossover treatment period.

Trial Locations

Locations (469): Kaiser Permanente - Deer Valley
🇺🇸
Antioch, California, United States
Alta Bates Summit Comprehensive Cancer Center
🇺🇸
Berkeley, California, United States
Peninsula Medical Center
🇺🇸
Burlingame, California, United States
East Bay Radiation Oncology Center
🇺🇸
Castro Valley, California, United States
Valley Medical Oncology Consultants - Castro Valley
🇺🇸
Castro Valley, California, United States
Cancer Care Center at John Muir Health - Concord Campus
🇺🇸
Concord, California, United States
Kaiser Permanente - Fremont
🇺🇸
Fremont, California, United States
Valley Medical Oncology
🇺🇸
Fremont, California, United States
Glendale Memorial Hospital Comprehensive Cancer Center
🇺🇸
Glendale, California, United States
Kaiser Permanente Medical Center - Hayward
🇺🇸
Hayward, California, United States
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Kaiser Permanente - Deer Valley
🇺🇸Antioch, California, United States