Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

Phase 3

Completed

Conditions: Myelodysplastic/Myeloproliferative Neoplasms
Lymphoma
Lymphoproliferative Disorder
Chronic Myeloproliferative Disorders
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Leukemia
Pain
Unspecified Adult Solid Tumor, Protocol Specific
Neurotoxicity

Interventions: Drug: baclofen/amitriptyline/ketamine gel
Other: placebo

Registration Number: NCT00516503

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary: RATIONALE: Baclofen-amitriptyline-ketamine (BAK) gel may lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether BAK gel is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy .

PURPOSE: This randomized phase III trial is studying BAK gel 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

* Compare the effectiveness of baclofen-amitriptyline hydrochloride-ketamine (BAK) gel versus placebo, in terms of improving sensory neuropathy, in cancer patients with chemotherapy-induced peripheral neuropathy\> Secondary\>

* Compare motor and autonomic symptoms and functioning, mood states, pain, and peripheral neuropathy in these patients.

* Assess the adverse event profile of topical BAK gel.

* Explore whether topical BAK gel is absorbed systemically. OUTLINE: Patients are stratified according to neurotoxic chemotherapy (active vs non-active), current use of opioids or oral pain medications (yes vs no), pain rating (4-7 vs 8-10), and prior ineffective pharmacologic treatment for peripheral neuropathy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.

* Arm II: Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.

Some patients in both arms may choose to continue on the active gel or, if on placebo, begin the active gel for an additional 8 weeks off study. Patients complete health, pain, mood, and quality of life questionnaires at baseline and periodically during study. Patients also record adverse symptoms weekly in a Symptom Experience Diary.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 208

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	baclofen/amitriptyline/ketamine gel	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel\> topically to each\> area of pain,\> numbness,\> and/or tingling\> on the\> feet and/or hands twice daily\> for\> 4 weeks.
Arm II	placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.

Primary Outcome Measures

Name	Time	Method
Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20]	From baseline to 4 weeks	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

Secondary Outcome Measures

Name	Time	Method
Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4	From Baseline to week 4	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0	Up to 4 weeks	Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.
Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks	Up to 4 weeks	The Peripheral Neuropathy Questionnaire was used to analyze this endpoint. Patient neuropathy symptoms were scored on a 0 - 100 scale (higher score represents less symptomatic). The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.
Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4	Up to 4 weeks	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the autonomic neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)	At 4 weeks	Each mood scale (0 - 100, higher is better mood) will be analyzed as an endpoint along with the total mood disturbance score.
Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4	Up to 4 weeks	Pain severity, defined by the four items addressing worst, least, and average pain and pain right now as measured by the BPI will be analyzed identical to the primary endpoint. Additionally, total pain interference as measured by the BPI will be transformed onto a 0-100 ( higher is less pain) point scale. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.

Trial Locations

Locations (162): Mayo Clinic Scottsdale
🇺🇸
Scottsdale, Arizona, United States
Mayo Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States
Rush-Copley Cancer Care Center
🇺🇸
Aurora, Illinois, United States
St. Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Graham Hospital
🇺🇸
Canton, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Eureka Community Hospital
🇺🇸
Eureka, Illinois, United States
Galesburg Clinic, PC
🇺🇸
Galesburg, Illinois, United States
Galesburg Cottage Hospital
🇺🇸
Galesburg, Illinois, United States
Mason District Hospital
🇺🇸
Havana, Illinois, United States
Scroll for more (152 remaining)
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States