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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Neurotoxicity, Pain, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: lamotrigine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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 Life expectancy At least 6 months 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: Chemotherapy See Disease Characteristics More than 7 days since prior methotrexate or other dihydrofolate inhibitors 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I - lamotrigine<br>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<br> <br> |
| Other: Arm II - placebo<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS) | The change in mean score for average daily pain from baseline to week 10 using the Pain Intensity Rating (NRS) are reported below. The NRS scale ranges from 0 to 10 with higher scores corresponding to having more pain. | From baseline to week 10 | 
| Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS) | The change in mean score for average daily pain from baseline to week 10 using the European Cooperative Oncology Group (ECOG) neuropathy scale (ENS) are reported below. The ENS scale goes from 0 to 3 with 0=none, 1=mild paresthesias, 2=mild or moderate sensory loss and/or moderate paresthesias, and 3=severe sensory loss or paresthesias that interfere with function. | From baseline to week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10 | The change in overall quality of life as measured by the Uniscale QOL (Week 10 minus Baseline) using the Wilcoxon test is reported for each arm below. The Uniscale is a score that ranges from 0 to 100, with 0 being QOL as bad as it can be and 100 being as good as it can be. | From baseline to week 10 | 
| Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Worst Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 | 
| Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Least Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. Time Frame: Up to 1 week post-treatment | From baseline to week 10 | 
| Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Average Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 | 
| Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Now scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 | 
| Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Relief scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 | 
| Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Interference scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 | 
| Change in POMS Total Score [Week 10 Minus Baseline] | The average change in POMS Total scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The POMS scales are calculated from patient responses on 30 questions asking how they have been feeling during the past week. The scores are all transformed so that 0 is the worst possible value and 100 is the best possible value. | From baseline to week 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurotoxicity, pain, unspecified adult solid tumor, protocol specific