Official Title: “The Use of Topical Baclofen, Amitriptyline HCI, and Ketamine (BAK) in a PLO Gel vs. Placebo for the Treatment of Chemotherapy Induced Peripheral Neuropathy: A Phase III Randomized Double-Blind Placebo Controlled Study”

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.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

Study Primary Completion Date: June 2009

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.

Intervention(s) in this Clinical Trial

• Drug: baclofen/amitriptyline/ketamine gel
  • Applied topically
• Drug: placebo
  • Applied topically

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 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.
• Placebo Comparator: 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.

Primary Measures

• Total sensory neuropathy (area under the curve [AUC]) as measured by the EORTC QLQ-CIPN20 at baseline and week 4

Secondary Measures

• Motor neuropathy as measured by the EORTC QLQ-CIPN20 at baseline and week 4
• Autonomic symptoms and functioning as measured by the EORTC QLQ-CIPN20 at baseline and week 4
• Mood states and total mood disturbance as measured by the Profile of Mood States-Brief at baseline and week 4
• Pain severity and interference as measured by the Brief Pain Inventory at baseline and week 4
• Numbness, tingling, and pain as measured by the Peripheral Neuropathy Questionnaire at baseline and weekly for 4 weeks
• Perception of benefit as measured by the Subject Global Impression of Change at the end of week 4
• 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

DISEASE CHARACTERISTICS:

• Diagnosis of cancer
• Received or currently receiving neurotoxic chemotherapy including, but not limited to, taxanes (e.g., paclitaxel or docetaxel); platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin); vinca alkaloids (e.g., vincristine or vinblastine); or other neurotoxic chemotherapy agents (e.g., bortezomib, lenalidomide, or thalidomide)
• Must have pain or symptoms of peripheral neuropathy attributable to chemotherapy for ≥ 1 month
• Neuropathy is limited to either hands and/or feet where gel can be applied
• Neuropathic pain score of ≥ 4 out of 10 on the numbness/tingling/pain numeric analogue scale
• No pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (e.g., diabetes, alcohol, toxin, heredity)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 4 months
• Creatinine ≤ 1.5 times upper limit of normal
• Not pregnant or nursing
• No ability to bear children defined by 1 of the criteria:
• Menopausal (12 months and no menstrual period if natural menopause)
• Underwent a hysterectomy and/or oophorectomy
• Permanent surgical sterilization (tubal ligation)
• Fertile patients must use effective contraception
• Able to complete questionnaires independently or with assistance
• Able to sign informed consent and understand the nature of a placebo-controlled trial
• No history of an allergic reaction to baclofen, amitriptyline hydrochloride, and/or ketamine
• No diagnosis of any New York Heart Association class I-IV congestive heart failure
• No diagnosis of coronary artery disease including, but not limited to, myocardial infarction, within the past 5 years
• No other medical condition that, in the opinion of the treating physician or allied health professional, would make this clinical trial unreasonably hazardous for the patient
• No skin abnormalities at the intended application sites (hands and feet) of study gel (i.e., skin breakdown)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 30 days since prior anticonvulsants, tricyclic antidepressants, monoamine oxidase inhibitor, or other neuropathic pain medication (e.g., carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, or amifostine)
• Patients treated with any of these agents for peripheral neuropathy for ≤ 1 week during the past 30 days are eligible provided they are no longer taking the agent
• More than 5 years since prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft
• Prior heart valve replacement surgery allowed provided patient has fully recovered from the surgery
• No concurrent use of study agents other than as specified in the trial

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Central Cancer Treatment Group

Overall Clinical Trial Officials and Contacts

Debra Barton, RN, PhD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00516503

Study ID Number: CDR0000560732

ClinicalTrials.gov Identifier: NCT00516503

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database