The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
18 Years
N/A
Both
Neurotoxicity, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Principal Investigator
Ravi D. Rao, MD, MBBS
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000322830
NCT ID:
NCT00068445
Start Date:
February 2004
Completion Date:
Related Keywords:
- Neurotoxicity
- Pain
- Unspecified Adult Solid Tumor, Protocol Specific
- neurotoxicity
- pain
- unspecified adult solid tumor, protocol specific
- Peripheral Nervous System Diseases
- Neurotoxicity Syndromes
Name | Location |
|---|---|
| Mayo Clinic Scottsdale | Scottsdale, Arizona 85259 |
| Mayo Clinic - Jacksonville | Jacksonville, Florida 32224 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| MBCCOP - Hawaii | Honolulu, Hawaii 96813 |
| CCOP - Upstate Carolina | Spartanburg, South Carolina 29303 |
| CCOP - Wichita | Wichita, Kansas 67214-3882 |
| CCOP - Atlanta Regional | Atlanta, Georgia 30342-1701 |
| CCOP - Missouri Valley Cancer Consortium | Omaha, Nebraska 68131 |
| CCOP - Illinois Oncology Research Association | Peoria, Illinois 61602 |
| CCOP - Carle Cancer Center | Urbana, Illinois 61801 |
| CCOP - Iowa Oncology Research Association | Des Moines, Iowa 50309-1016 |
| CCOP - Metro-Minnesota | Saint Louis Park, Minnesota 55416 |
| CCOP - Michigan Cancer Research Consortium | Ann Arbor, Michigan 48106 |
| CCOP - Duluth | Duluth, Minnesota 55805 |
| CCOP - Cedar Rapids Oncology Project | Cedar Rapids, Iowa 52403-1206 |
| Rapid City Regional Hospital | Rapid City, South Dakota 57709 |
| CCOP - Sioux Community Cancer Consortium | Sioux Falls, South Dakota 57105-1080 |
| CCOP - Dayton | Kettering, Ohio 45429 |
| CCOP - St. Vincent Hospital Cancer Center, Green Bay | Green Bay, Wisconsin 54301 |
| CCOP - Toledo Community Hospital | Toledo, Ohio 43623-3456 |
| Coborn Cancer Center | Saint Cloud, Minnesota 56303 |
| Cancer Care Center at Medcenter One Hospital | Bismarck, North Dakota 58501 |
| Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center | Sioux City, Iowa 51101 |
