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Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
First Received: May 8, 2007   Last Updated: April 29, 2009   History of Changes
Sponsors and Collaborators: University of Rochester
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00471445
  Purpose

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.


Condition Intervention Phase
Cancer-Related Problem/Condition
Pain
Unspecified Adult Solid Tumor, Protocol Specific
Drug: ketamine/amitriptyline NP-H cream
Other: placebo
Phase III

MedlinePlus related topics: Cancer Peripheral Nerve Disorders
Drug Information available for: Amitriptyline Amitriptyline hydrochloride Ketamine hydrochloride Ketamine Triavil
U.S. FDA Resources
Study Type: Interventional
Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control
Official Title: Assessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Change in average daily peripheral neuropathy intensity score from baseline to week 6 in patients treated with amitriptyline and ketamine hydrochloride vs placebo [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients treated with amitriptyline and ketamine hydrochloride vs placebo whose CPN intensity decreases by ≥ 30% [ Designated as safety issue: No ]
  • Percentage of patients with ≥ 50% reduction in the level of peripheral neuropathy [ Designated as safety issue: No ]
  • Percentage of patients with continuous proportion of responder distribution function [ Designated as safety issue: No ]
  • Change in average daily pain, numbness, or tingling score from baseline to the end of treatment [ Designated as safety issue: No ]
  • Quality of sleep scores [ Designated as safety issue: No ]
  • Quality of pain as measured by the European Organization for Research and Treatment of Cancer Quality of Life-Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20) [ Designated as safety issue: No ]
  • Health-related quality of life as measured by the Brief Pain Inventory Interference Scale and Hamilton Anxiety and Depression Scale [ Designated as safety issue: No ]
  • Overall assessment of change since beginning of treatment, including changes in pain, side effects, functional status, and overall satisfaction with treatment as measured by the Patient Global Impression of Change Questionnaire [ Designated as safety issue: No ]
  • Comparison of proportion of patients in each arm who decide to continue treatment beyond week 6 [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: October 2007
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental
Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
Drug: ketamine/amitriptyline NP-H cream
Applied topically
Arm II: Placebo Comparator
Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
Other: placebo
Applied topically

Detailed Description:

OBJECTIVES:

  • Compare the analgesic properties and safety of topical amitriptyline and ketamine hydrochloride cream vs placebo in cancer patients with chemotherapy peripheral neuropathy (CPN) who have received taxanes or other cancer chemotherapy agents.

OUTLINE: This is a multicenter, double-blind, randomized, placebo-controlled study. Patients are stratified according to Community Clinical Oncology Program (CCOP) site. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
  • Arm II: Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.

In both arms, treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to a total of 12 weeks.

Patients complete a peripheral neuropathy intensity and quality of sleep diary daily. Patients also complete the European Organization for Research and Treatment of Cancer Quality of Life-Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20) to assess change in sensory score and the Brief Pain Inventory and Hospital Anxiety and Depression Scale to assess health-related quality of life in week 3 and 6. The VES-13 is administered at baseline to assess level of physical activity and the URCC symptom inventory is administered to track other potentially important symptoms. The Patient Global Impression of Change Questionnaire is administered in week 6 to assess the patient's overall assessment of change since beginning treatment, including changes in pain, side effects, functional status, and overall satisfaction with treatment.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 concuurent 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00471445

Locations
United States, New York
University of Rochester Cancer Center CCOP Research Base Recruiting
Rochester, New York, United States, 14642
Contact: Gary R. Morrow, PhD, MS     585-275-5513        
Sponsors and Collaborators
University of Rochester
Investigators
Study Chair: Supriya Mohile, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: James P. Wilmot Cancer Center at University of Rochester Medical Center ( Gary R. Morrow )
Study ID Numbers: CDR0000543103, URCC-0605, URCC-07004
Study First Received: May 8, 2007
Last Updated: April 29, 2009
ClinicalTrials.gov Identifier: NCT00471445     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
pain
neurotoxicity

Study placed in the following topic categories:
Anesthetics, Intravenous
Excitatory Amino Acids
Neurotransmitter Agents
Neurotoxicity Syndromes
Adrenergic Agents
Psychotropic Drugs
Central Nervous System Depressants
Anesthetics
Pain
Anesthetics, Dissociative
Antidepressive Agents, Tricyclic
Neuromuscular Diseases
Anesthetics, General
Analgesics, Non-Narcotic
Peripheral Nervous System Diseases
Ketamine
Amitriptyline
Analgesics
Peripheral Nervous System Agents
Antidepressive Agents

Additional relevant MeSH terms:
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Physiological Effects of Drugs
Psychotropic Drugs
Anesthetics
Excitatory Amino Acid Agents
Neuromuscular Diseases
Sensory System Agents
Therapeutic Uses
Ketamine
Analgesics
Antidepressive Agents
Excitatory Amino Acid Antagonists
Anesthetics, Intravenous
Nervous System Diseases
Central Nervous System Depressants
Pharmacologic Actions
Anesthetics, Dissociative
Antidepressive Agents, Tricyclic
Analgesics, Non-Narcotic
Anesthetics, General
Peripheral Nervous System Diseases
Amitriptyline
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 07, 2009