Clinical trial NCT00471445: Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
Official title: Assessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neurotoxicity
Pain
Peripheral Neuropathy
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
pain
neurotoxicity
peripheral neuropathy
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-10
Enrollment: 462
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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, 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

Primary outcomes:
measure: Change in Average Daily Peripheral Neuropathy Intensity Score From Baseline to Week 6 in Patients Treated With Amitriptyline and Ketamine Hydrochloride vs Placebo
timeFrame: Week 6 - Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: MBCCOP - Hawaii
state: Hawaii
city: Chicago
country: United States
facility: MBCCOP - University of Illinois at Chicago
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: St. Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
Study officials:
affiliation: James P. Wilmot Cancer Center
name: Supriya Mohile, MD
role: STUDY_CHAIR
References:
citation: 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.