Official Title: “The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial”

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.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

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.

Intervention(s) in this Clinical Trial

• Drug: lamotrigine
• Procedure: quality-of-life assessment

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Central Cancer Treatment Group

Overall Clinical Trial Officials and Contacts

Ravi D. Rao, MD, MBBS Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00068445

Study ID Number: CDR0000322830

ClinicalTrials.gov Identifier: NCT00068445

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database