Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
Condition: Neurotoxicity; Pain; Peripheral Neuropathy; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Peripheral Nervous System Diseases; Neurotoxicity Syndromes
Intervention: ketamine/amitriptyline NP-H cream; placebo
Intervention description: Subjects were instructed to apply up to, but not exceeding, 4 g of ketamine/amitriptyline NP-H cream two times per day to each area with pain, numbness, and/or tingling. A measuring device was provided to assist in dispensing the proper amount of the cream.; Applied topically
Intervention MeSH terms: Ketamine; Amitriptyline
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 462.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: unspecified adult solid tumor, protocol specific; pain; neurotoxicity; peripheral neuropathy

Summary:

      RATIONALE: Topical cream containing amitriptyline and ketamine may help relieve pain,
      numbness, tingling, and other symptoms of peripheral neuropathy. It is not yet known whether
      topical amitriptyline and ketamine cream is more effective than a placebo in treating
      peripheral neuropathy caused by chemotherapy.

      PURPOSE: This randomized phase III trial is studying the side effects and how well topical
      amitriptyline and ketamine cream work compared with a placebo in treating peripheral
      neuropathy caused by chemotherapy in patients with cancer.
    

Eligibility 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, 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 ≤ 1,800 mg per day

               -  Pregabalin dose ≤ 300 mg per day

               -  Opioid analgesic dose ≤ 60 mg oxycodone hydrochloride equivalent per day

               -  Tricyclic antidepressant dose ≤ 75 mg amitriptyline equivalent per day

               -  Duloxetine dose ≤ 60 mg per day

               -  Venlafaxine dose ≤ 150 mg per day

               -  Tramadol dose ≤ 200 mg per day

          -  Concurrent adjunctive analgesic therapy, such as acupuncture, biofeedback, or herbal
             preparations, allowed provided dose has been stable for ≥ 2 weeks