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: Randomized phase III trial to study the effectiveness of lamotrigine in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy caused by chemotherapy in patients who have cancer.

Condition	Treatment or Intervention	Phase
Quality of Life neurotoxicity Pain unspecified adult solid tumor, protocol specific	Drug: lamotrigine  Procedure: chemoprotection  Procedure: complications of therapy assessment/management  Procedure: neurotoxicity attenuation  Procedure: pain therapy  Procedure: quality-of-life assessment  Procedure: supportive care/therapy	Phase III

Further Study Details: 

OBJECTIVES:

• 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.

• Arm I: Patients receive oral lamotrigine once daily for 2 weeks and then twice daily for 8 weeks.
• Arm II: Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks. In both arms, 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.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Not specified

Life expectancy

• At least 6 months

Hematopoietic

• Not specified

Hepatic

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

Renal

• Creatinine ≤ 1.5 times ULN

Other

• 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

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

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

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• 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

Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
Michigan
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Coborn Cancer Center, Saint Cloud,  Minnesota,  56303,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
North Dakota
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States; Recruiting
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting

Study chairs or principal investigators

Gilbert Wong, MD,  Study Chair,  Mayo Clinic Cancer Center   
Charles L. Loprinzi, MD,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000322830; NCCTG-N01C3; NCT00068445
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  September 10, 2003
ClinicalTrials.gov Identifier:  NCT00068445
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08