Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gary Morrow, University of Rochester
ClinicalTrials.gov Identifier:
NCT00471445
First received: May 8, 2007
Last updated: January 31, 2014
Last verified: January 2014
  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
Neurotoxicity
Pain
Peripheral Neuropathy
Unspecified Adult Solid Tumor, Protocol Specific
Drug: ketamine/amitriptyline NP-H cream
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Assessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)

Resource links provided by NLM:


Further study details as provided by University of Rochester:

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 [ Time Frame: 6 weeks ] [ 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% [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with ≥ 50% reduction in the level of peripheral neuropathy [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with continuous proportion of responder distribution function [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Change in average daily pain, numbness, or tingling score from baseline to the end of treatment [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Quality of sleep scores [ Time Frame: 6 weeks ] [ 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) [ Time Frame: 6 weeks ] [ 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 [ Time Frame: 6 weeks ] [ 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 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Comparison of proportion of patients in each arm who decide to continue treatment beyond week 6 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: October 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: ketamine/amitriptyline NP-H cream
Applied topically
Placebo Comparator: Arm II
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-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 Vulnerable Elders Survey (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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471445

Locations
United States, Hawaii
MBCCOP - Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
MBCCOP - University of Illinois at Chicago
Chicago, Illinois, United States, 60612-7323
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
CCOP - Evanston
Evanston, Illinois, United States, 60201
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Michigan
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
CCOP - Metro-Minnesota
St. Louis Park, Minnesota, United States, 55416
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New York
CCOP - Hematology-Oncology Associates of Central New York
East Syracuse, New York, United States, 13057
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
United States, North Carolina
CCOP - Southeast Cancer Control Consortium
Winston-Salem, North Carolina, United States, 27104-4241
United States, Oregon
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
United States, South Carolina
CCOP - Greenville
Greenville, South Carolina, United States, 29615
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
United States, Washington
CCOP - Virginia Mason Research Center
Seattle, Washington, United States, 98101
CCOP - Northwest
Tacoma, Washington, United States, 98405-0986
United States, Wisconsin
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
Sponsors and Collaborators
Gary Morrow
Investigators
Study Chair: Supriya Mohile, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
No publications provided by University of Rochester

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gary Morrow, Director, URCC CCOP Research Base, University of Rochester
ClinicalTrials.gov Identifier: NCT00471445     History of Changes
Other Study ID Numbers: CDR0000543103, U10CA037420, URCC-0605, URCC-07004
Study First Received: May 8, 2007
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Rochester:
unspecified adult solid tumor, protocol specific
pain
neurotoxicity
peripheral neuropathy

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

ClinicalTrials.gov processed this record on September 30, 2014