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

NCT00471445 | Completed Phase 3 Results DMC

• 4 other identifiers: CDR0000543103U10CA037420URCC-0605URCC07004
• Study Type: interventional
• Target: 462
• Locations: 1 country
• Sites: 17

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.

Conditions

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

Keywords

unspecified adult solid tumor, protocol specific; pain; neurotoxicity; peripheral neuropathy

Outcome Measures

Primary Outcomes (1)

• Change in Average Daily Peripheral Neuropathy Intensity Score From Baseline to Week 6 in Patients Treated With Amitriptyline and Ketamine Hydrochloride vs Placebo

  Cancer survivors who completed chemotherapy at least 1 month prior and had Chemotherapy Induced Peripheral Neuropathy (CIPN) (greater than or equal to 4 out of 10) were enrolled. CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in their hands and feet over the past 24 hours" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. CIPN ranges from 0 (no pain) to 10 (worst possible pain).

  Week 6 - Baseline

Study Arms (2)

ketamine/amitriptyline NP-H cream

EXPERIMENTAL

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.

Drug: ketamine/amitriptyline NP-H cream

Placebo Cream

PLACEBO COMPARATOR

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

Other: placebo

Interventions

ketamine/amitriptyline NP-H cream 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.

Also known as: EpiCept NP-1

ketamine/amitriptyline NP-H cream

placebo OTHER

Applied topically

Placebo Cream

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Gary Morrow: lead
• National Cancer Institute (NCI): collaborator

Study Sites (17)

MBCCOP - Hawaii

Honolulu, Hawaii, 96813, United States

Location

MBCCOP - University of Illinois at Chicago

Chicago, Illinois, 60612-7323, United States

Location

CCOP - Central Illinois

Decatur, Illinois, 62526, United States

Location

CCOP - Evanston

Evanston, Illinois, 60201, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214-3882, United States

Location

CCOP - Grand Rapids

Grand Rapids, Michigan, 49503, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

CCOP - Hematology-Oncology Associates of Central New York

East Syracuse, New York, 13057, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, 27104-4241, United States

Location

CCOP - Columbia River Oncology Program

Portland, Oregon, 97225, United States

Location

CCOP - Greenville

Greenville, South Carolina, 29615, United States

Location

CCOP - Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

CCOP - Virginia Mason Research Center

Seattle, Washington, 98101, United States

Location

CCOP - Northwest

Tacoma, Washington, 98405-0986, United States

Location

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, 54449, United States

Location

Related Publications (1)

• 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.

  PMID: 24531792 DERIVED

MeSH Terms

Conditions

Neurotoxicity Syndromes; Pain; Peripheral Nervous System Diseases

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Since ketamine and amitriptyline are both analgesics, it is possible that the effects of the ketamine plus amitriptyline-containing creams may have been diluted when all three neuropathy symptoms were assessed together.

Results Point of Contact

• Title: Charles E. Heckler, PhD, MS. Research Assistant Professor
• Organization: University of Rochester Medical Center

checkler@urmc.rochester.edu

585-273-1141

Study Officials

• Supriya Mohile, MD

  James P. Wilmot Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, URCC NCORP Research Base

Study Record Dates

• First Submitted: May 8, 2007
• First Posted: May 10, 2007
• Study Start: October 1, 2007
• Primary Completion: September 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 9, 2015
• Results First Posted: June 10, 2015

Record last verified: 2015-10

Locations

US (17)