Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care	Active	18 and over	NCI	URCC-0605 URCC-07004, URCC-06-05, NCT00471445

Objectives

1. 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.

Entry 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 concuurent active chemotherapy in the adjuvant setting or for progressive systemic disease

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

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

Expected Enrollment

A total of 400 patients will be accrued for this study.

Outcomes

Change in average daily peripheral neuropathy intensity score from baseline to week 6 in patients treated with amitriptyline and ketamine hydrochloride vs placebo

Percentage of patients treated with amitriptyline and ketamine hydrochloride vs placebo whose CPN intensity decreases by ≥ 30%
Percentage of patients with ≥ 50% reduction in the level of peripheral neuropathy
Percentage of patients with continuous proportion of responder distribution function
Change in average daily pain, numbness, or tingling score from baseline to the end of treatment
Quality of sleep scores
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)
Health-related quality of life as measured by the Brief Pain Inventory Interference Scale and Hamilton Anxiety and Depression Scale
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
Comparison of proportion of patients in each arm who decide to continue treatment beyond week 6

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 QLQ-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 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.

Trial Contact Information

Trial Lead Organizations

University of Rochester Cancer Center CCOP Research Base

Supriya Mohile, MD, Protocol chair		Ph: 585-275-5513

U.S.A.
Hawaii
	Honolulu
	MBCCOP - Hawaii
		James Tom	Ph:  808-586-2979
Illinois
	Chicago
	MBCCOP - University of Illinois at Chicago
		Judith Murray	Ph:  312-355-1472
			Email: memurray@uic.edu
	Decatur
	CCOP - Central Illinois
		Peggy Verrill	Ph:  217-876-6618
			Email: peggyv@dmhhs.org
	Evanston
	CCOP - Evanston
		Michelle Britto	Ph:  847-570-2109
Kansas
	Wichita
	CCOP - Wichita
		Marge Good	Ph:  316-268-5784
			Email: marge_good@via-christi.org
Michigan
	Grand Rapids
	CCOP - Grand Rapids
		Connie Szczepanek	Ph:  616-391-1230
Minnesota
	St. Louis Park
	CCOP - Metro-Minnesota
		Marilee Rose	Ph:  952-993-1516
Nevada
	Las Vegas
	CCOP - Nevada Cancer Research Foundation
		Karen Sartell	Ph:  702-384-0013
New York
	East Syracuse
	CCOP - Hematology-Oncology Associates of Central New York
		Colleen Sweeney	Ph:  315-472-7504 ext. 2129
	Manhasset
	CCOP - North Shore University Hospital
		Nanette Nier-Shoulson, RN	Ph:  516-734-8918
			Email: nnier@nshs.edu
North Carolina
	Winston-Salem
	CCOP - Southeast Cancer Control Consortium
		Robin Burgess	Ph:  336-777-3036
Oregon
	Portland
	CCOP - Columbia River Oncology Program
		Mary Brunetti	Ph:  503-216-6262
South Carolina
	Greenville
	CCOP - Greenville
		Lyndon Evans, RN	Ph:  864-404-2045
	Spartanburg
	CCOP - Upstate Carolina
		Nancy Sprouse	Ph:  864-560-6812
Washington
	Seattle
	CCOP - Virginia Mason Research Center
		Beth Edelhert	Ph:  206-341-0446
	Tacoma
	CCOP - Northwest
		Karyn Hart	Ph:  253-403-1461
			Email: karyn.hart@multicare.org
Wisconsin
	Marshfield
	CCOP - Marshfield Clinic Research Foundation
		Cheryl Esselman	Ph:  715-389-5153

Registry Information
Official Title		Assessment of Topical Treatment Response with Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)
Trial Start Date		2007-10-25
Trial Completion Date		2010-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00471445
Date Submitted to PDQ		2007-04-05
Information Last Verified		2009-08-20

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