Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00068445
Recruitment Status : Completed
First Posted : September 11, 2003
Last Update Posted : July 14, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief Summary:

RATIONALE: Lamotrigine may be effective in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy. It is not yet known whether lamotrigine is effective in treating peripheral neuropathy caused by chemotherapy.

PURPOSE: This randomized phase III trial is studying how well lamotrigine works in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy caused by chemotherapy in patients with cancer.

Condition or disease Intervention/treatment Phase
Neurotoxicity Pain Unspecified Adult Solid Tumor, Protocol Specific Drug: lamotrigine Other: Placebo Phase 3

Detailed Description:


  • Compare the efficacy of lamotrigine vs placebo in reducing pain and symptoms of chemotherapy-induced peripheral neuropathy in patients with cancer.
  • Compare symptom distress, mood states, functional abilities, and overall quality of life of patients treated with these agents.
  • Determine the toxic effects of lamotrigine in these patients.

OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to neurotoxic chemotherapy received (taxanes vs platinum-based compounds vs vinca alkaloids vs combination vs other), status of neurotoxic chemotherapy (actively receiving therapy vs discontinued or completed), and duration of pain or neuropathy symptoms (1-3 months vs 3-6 months vs more than 6 months). Patients are randomized to 1 of 2 treatment arms.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
Study Start Date : February 2004
Actual Primary Completion Date : May 2006
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Lamotrigine
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Arm I - lamotrigine

Patients receive oral lamotrigine once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks in the absence of unacceptable toxicity.

Quality of life, pain, mood states, and symptom distress are assessed at baseline and at 4, 6, 8, and 10 weeks.

Patients are followed at 3-7 days.

Drug: lamotrigine
Arm II - placebo

Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks.

Treatment continues for 10 weeks in the absence of unacceptable toxicity.

Quality of life, pain, mood states, and symptom distress are assessed at baseline and at 4, 6, 8, and 10 weeks.

Patients are followed at 3-7 days.

Other: Placebo

Primary Outcome Measures :
  1. Reduction of pain and symptoms of chemotherapy-induced peripheral neuropathy [ Time Frame: Up to 1 week post-treatment ]

Secondary Outcome Measures :
  1. Overall quality of life [ Time Frame: Up to 1 week post-treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of cancer
  • Received, or are currently receiving, neurotoxic chemotherapy, including any of the following:

    • Taxanes (e.g., paclitaxel or docetaxel)
    • Platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin)
    • Vinca alkaloids (e.g., vincristine or vinblastine)
  • Experiencing pain or symptoms of peripheral neuropathy for at least 1 month attributed to chemotherapy

    • Average daily pain rating of at least 4 out of 10 OR
    • Peripheral neuropathy at least grade 1 out of 3 using ECOG sensory neuropathy rating



  • 18 and over

Life expectancy

  • At least 6 months


  • Bilirubin < 2 times upper limit of normal (ULN)


  • Creatinine ≤ 1.5 times ULN


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior allergic reaction or intolerance to lamotrigine
  • No extreme difficulty swallowing pills
  • No other identified causes of painful paresthesia preceding chemotherapy, including any of the following:

    • Radiation or malignant plexopathy
    • Lumbar or cervical radiculopathy
    • Pre-existing peripheral neuropathy of another etiology, such as any of the following:

      • Cyanocobalamin deficiency
      • AIDS
      • Monoclonal gammopathy
      • Diabetes
      • Heavy metal poisoning amyloidosis
      • Syphilis
      • Hyperthyroidism or hypothyroidism
      • Inherited neuropathy
  • No significant psychiatric illness (e.g., mania, psychosis, or schizophrenia) that would preclude study participation
  • Able to complete questionnaires



  • See Disease Characteristics
  • More than 7 days since prior methotrexate or other dihydrofolate inhibitors


  • More than 7 days since prior, and no concurrent use of any of the following:

    • Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, or desipramine)

      • Concurrent selective serotonin reuptake inhibitors allowed
    • Monoamine oxidase inhibitors
    • Opioid analgesics
    • Anticonvulsants (e.g., gabapentin, topiramate, valproic acid, or clonazepam)
    • Adjuvant analgesics (e.g., mexiletine)

      • Prior nonsteroidal anti-inflammatory drugs allowed
    • Topical analgesics (e.g., lidocaine gel or patch) to the affected area
    • Amifostine
  • More than 30 days since prior investigational agents for pain control
  • No other concurrent investigational agents for pain control

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00068445

  Hide Study Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Georgia
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342-1701
United States, Hawaii
MBCCOP - Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615-7828
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1854
Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center
Sioux City, Iowa, United States, 51101-1733
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Michigan
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
United States, Minnesota
CCOP - Duluth
Duluth, Minnesota, United States, 55805
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Coborn Cancer Center
Saint Cloud, Minnesota, United States, 56303
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, North Dakota
Cancer Care Center at Medcenter One Hospital
Bismarck, North Dakota, United States, 58501-5505
United States, Ohio
CCOP - Dayton
Dayton, Ohio, United States, 45429
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43623-3456
United States, South Carolina
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
United States, South Dakota
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54301
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Ravi D. Rao, MD, MBBS Mayo Clinic

Publications of Results:
Renno SI, Rao RD, Sloan J, et al.: The efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase III randomized, double blind, placebo-controlled NCCTG trial, N01C3. [Abstract] J Clin Oncol 24 (Suppl 18): A-8530, 475s, 2006.

Responsible Party: Alliance for Clinical Trials in Oncology Identifier: NCT00068445     History of Changes
Other Study ID Numbers: NCCTG-N01C3
CDR0000322830 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: September 11, 2003    Key Record Dates
Last Update Posted: July 14, 2016
Last Verified: July 2016

Keywords provided by Alliance for Clinical Trials in Oncology:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Peripheral Nervous System Diseases
Neurotoxicity Syndromes
Neuromuscular Diseases
Nervous System Diseases
Chemically-Induced Disorders
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers