Assessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- History of cancer

- Pain, numbness, or tingling in the hands or feet beginning in association with a
cancer chemotherapy agent (taxane or other chemotherapeutic agent) and persisting for
at least 28 days following the conclusion of chemotherapy

- Pain, numbness, or tingling can be assessed 28 days or more after the conclusion
of chemotherapy

- An average score of ≥ 4 for the 7 daily ratings of the baseline week on the
11-point rating scale of peripheral neuropathy associated with chemotherapy,
with a minimum of 5 daily diary ratings completed during the baseline week

- No preexisting or history of peripheral neuropathy due to any cause other than
chemotherapy (e.g., hereditary condition, alcohol, or diabetes)

- Patients with stable systemic metastases and/or bone involvement AND has not received
chemotherapy within 3 months of screening assessment are eligible

- Patients receiving ongoing treatment with non-chemotherapy agents (e.g.,
monoclonal antibodies or hormonal treatment) allowed

- No concurrent active chemotherapy in the adjuvant setting or for progressive systemic
disease

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Creatinine ≤ 2 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to adequately understand English

- No allergy or hypersensitivity to ketamine hydrochloride or amitriptyline or any of
the components of study drug

- No clinically significant illness (e.g., endocrine, cardiac, hepatic, renal,
neurologic, hematologic, or skeletal illness) that, in the investigator's clinical
judgment, could interfere with the efficacy or safety assessments in this study

- No glaucoma or recurrent urinary retention

- No clinically significant depression or dementia that, in the opinion of the
investigator, may interfere with a patient's adherence to the study protocol and/or
the accurate and consistent reporting of CPN

- No open skin lesions in the area where the cream is to be applied

- No HIV positivity

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 30 days since prior unapproved experimental drugs or biological agents

- No prior topical treatment, nerve blocks, implantable therapy, peripheral nerve or
spinal cord stimulation, or neurosurgical procedure for chemotherapy-related
peripheral neuropathy (CPN)

- No prior exposure to a peripheral neurotoxin other than chemotherapy

- No concurrent medications (e.g., phenytoin) known to be associated with sensory
neuropathy

- No concurrent selective serotonin reuptake inhibitors (e.g., fluoxetine, paroxetine,
or sertraline), which inhibit CP450 2D6, unless the patient is being treated for
depression or another psychiatric disorder and, in the investigator's judgment, the
patient's participation in the study can be permitted given the minimal systemic
levels of amitriptyline found within the cream

- No concurrent monoamine oxidase inhibitors, barbiturates, anticholinergic agents, or
sympathomimetic drugs, including epinephrine combined with local anesthetics

- Oral inhalers that include any of the drugs listed above are allowed

- Concurrent opioid analgesics, tricyclic or dual reuptake inhibitor antidepressants,
or gabapentin or pregabalin for CPN, or benzodiazepines for sleep allowed, provided
dose has been stable for ≥ 2 weeks and the following are true:

- Gabapentin dose must be ≤ 1,800 mg per day

- Pregabalin dose must be ≤ 300 mg per day

- Opioid analgesic dose must be ≤ 60 mg of oxycodone hydrochloride equivalent per
day

- Tricyclic antidepressant dose must be ≤ 75 mg amitriptyline equivalent per day

- Duloxetine dose must be ≤ 60 mg per day

- Venlafaxine dose must be ≤ 150 mg per day

- Tramadol dose must be ≤ 200 mg per day

- Concurrent adjunctive analgesic therapy, such as acupuncture, biofeedback, or herbal
preparations, allowed provided dose has been stable for ≥ 2 weeks