Know Cancer

forgot password

Assessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)

Phase 3
18 Years
Open (Enrolling)
Neurotoxicity, Pain, Peripheral Neuropathy, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

Assessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)


- 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 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.

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

Inclusion Criteria


- 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


- 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


- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care

Outcome Measure:

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

Outcome Time Frame:

6 weeks

Safety Issue:


Principal Investigator

Supriya Mohile, MD

Investigator Role:

Study Chair

Investigator Affiliation:

James P. Wilmot Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2007

Completion Date:

December 2013

Related Keywords:

  • Neurotoxicity
  • Pain
  • Peripheral Neuropathy
  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • pain
  • neurotoxicity
  • peripheral neuropathy
  • Peripheral Nervous System Diseases
  • Neurotoxicity Syndromes
  • Demyelinating Diseases
  • Polyneuropathies
  • Nerve Compression Syndromes
  • Neurologic Manifestations



MBCCOP - Hawaii Honolulu, Hawaii  96813
CCOP - Upstate Carolina Spartanburg, South Carolina  29303
CCOP - Wichita Wichita, Kansas  67214-3882
CCOP - North Shore University Hospital Manhasset, New York  11030
CCOP - Southeast Cancer Control Consortium Winston-Salem, North Carolina  27104-4241
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
CCOP - Central Illinois Springfield, Illinois  62526
CCOP - Greenville Greenville, South Carolina  29615
MBCCOP - University of Illinois at Chicago Chicago, Illinois  60612
CCOP - Evanston Evanston, Illinois  60201
CCOP - Grand Rapids Grand Rapids, Michigan  49503
CCOP - Columbia River Oncology Program Portland, Oregon  97225
CCOP - Virginia Mason Research Center Seattle, Washington  98101
CCOP - Northwest Tacoma, Washington  98405-0986
CCOP - Marshfield Clinic Research Foundation Marshfield, Wisconsin  54449
CCOP - Hematology-Oncology Associates of Central New York East Syracuse, New York  13057
CCOP - Nevada Cancer Research Foundation Las Vegas, Nevada  89109-2306