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

NCT ID: NCT00471445

Last Updated: 2015-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 462 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2013-11-30

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 University of Rochester Cancer Center (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 462 patients will be accrued for this study.

Conditions

Neurotoxicity; Pain; Peripheral Neuropathy; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

ketamine/amitriptyline NP-H cream

Patients apply 4 grams amitriptyline (4%) and ketamine (2%) hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.

Group Type: EXPERIMENTAL

ketamine/amitriptyline NP-H cream

Intervention Type: DRUG

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.

Placebo Cream

Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Applied topically

Interventions

ketamine/amitriptyline NP-H cream

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.

Intervention Type: DRUG

placebo

Applied topically

Intervention Type: OTHER

Other Intervention Names

EpiCept NP-1

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Gary Morrow

OTHER

Sponsor Role: lead

Responsible Party

Gary Morrow

Director, URCC NCORP Research Base

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Supriya Mohile, MD

Role: STUDY_CHAIR

James P. Wilmot Cancer Center

Locations

MBCCOP - Hawaii

Honolulu, Hawaii, United States

MBCCOP - University of Illinois at Chicago

Chicago, Illinois, United States

CCOP - Central Illinois

Decatur, Illinois, United States

CCOP - Evanston

Evanston, Illinois, United States

CCOP - Wichita

Wichita, Kansas, United States

CCOP - Grand Rapids

Grand Rapids, Michigan, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

CCOP - Hematology-Oncology Associates of Central New York

East Syracuse, New York, United States

CCOP - North Shore University Hospital

Manhasset, New York, United States

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

CCOP - Greenville

Greenville, South Carolina, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

CCOP - Northwest

Tacoma, Washington, United States

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States

Countries

United States

References

Gewandter JS, Mohile SG, Heckler CE, Ryan JL, Kirshner JJ, Flynn PJ, Hopkins JO, Morrow GR. A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors. Support Care Cancer. 2014 Jul;22(7):1807-14. doi: 10.1007/s00520-014-2158-7. Epub 2014 Feb 16.

Reference Type: DERIVED

PMID: 24531792 (View on PubMed)

Other Identifiers

U10CA037420

Identifier Type: NIH

Identifier Source: secondary_id

View Link

URCC-0605

Identifier Type: OTHER

Identifier Source: secondary_id

URCC07004

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000543103

Identifier Type: -

Identifier Source: org_study_id