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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00068445
• Other study ID #: NCCTG-N01C3
• Secondary ID: CDR0000322830
• Status: Completed
• Phase: Phase 3
• Start date: February 2004
• Est. completion date: November 2013

Study information

• Verified date: April 2018
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: November 2013
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neurotoxicity
• Neurotoxicity Syndromes
• Pain
• Peripheral Nervous System Diseases
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• lamotrigine

Other:
• Placebo

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Cancer Care Center at Medcenter One Hospital	Bismarck	North Dakota
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	CCOP - Dayton	Dayton	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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, 475

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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