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

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.

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