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

Overview[ - collapse ][ - ]

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.
ConditionNeurotoxicity
Pain
Peripheral Neuropathy
Unspecified Adult Solid Tumor, Protocol Specific
InterventionDrug: ketamine/amitriptyline NP-H cream
Other: placebo
PhasePhase 3
SponsorGary Morrow
Responsible PartyUniversity of Rochester
ClinicalTrials.gov IdentifierNCT00471445
First ReceivedMay 8, 2007
Last UpdatedJanuary 31, 2014
Last verifiedJanuary 2014

Tracking Information[ + expand ][ + ]

First Received DateMay 8, 2007
Last Updated DateJanuary 31, 2014
Start DateOctober 2007
Estimated Primary Completion DateDecember 2014
Current Primary Outcome MeasuresChange 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]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief TitleTopical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
Official TitleAssessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)
Brief 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.
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.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care
Condition
  • Neurotoxicity
  • Pain
  • Peripheral Neuropathy
  • Unspecified Adult Solid Tumor, Protocol Specific
InterventionDrug: ketamine/amitriptyline NP-H cream
Applied topically
Other: placebo
Applied topically
Study Arm (s)
  • 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.
  • Placebo Comparator: Arm II
    Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment400
Estimated Completion DateDecember 2014
Estimated Primary Completion DateAugust 2014
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 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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00471445
Other Study ID NumbersCDR0000543103
Has Data Monitoring CommitteeNot Provided
Information Provided ByUniversity of Rochester
Study SponsorGary Morrow
CollaboratorsNational Cancer Institute (NCI)
Investigators Study Chair: Supriya Mohile, MD James P. Wilmot Cancer Center
Verification DateJanuary 2014

Locations[ + expand ][ + ]

MBCCOP - Hawaii
Honolulu, Hawaii, United States, 96813
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
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
CCOP - Metro-Minnesota
St. Louis Park, Minnesota, United States, 55416
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
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
CCOP - Southeast Cancer Control Consortium
Winston-Salem, North Carolina, United States, 27104-4241
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
CCOP - Greenville
Greenville, South Carolina, United States, 29615
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
CCOP - Virginia Mason Research Center
Seattle, Washington, United States, 98101
CCOP - Northwest
Tacoma, Washington, United States, 98405-0986
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449