Back to resultsLamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
Primary Purpose
Neurotoxicity, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
lamotrigine
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Neurotoxicity focused on measuring neurotoxicity, pain, unspecified adult solid tumor, protocol specific
Eligibility 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 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
Sites / Locations
- Mayo Clinic Scottsdale
- Mayo Clinic - Jacksonville
- CCOP - Atlanta Regional
- MBCCOP - Hawaii
- CCOP - Illinois Oncology Research Association
- CCOP - Carle Cancer Center
- CCOP - Cedar Rapids Oncology Project
- CCOP - Iowa Oncology Research Association
- Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center
- CCOP - Wichita
- CCOP - Michigan Cancer Research Consortium
- CCOP - Duluth
- Mayo Clinic Cancer Center
- Coborn Cancer Center
- CCOP - Metro-Minnesota
- CCOP - Missouri Valley Cancer Consortium
- Cancer Care Center at Medcenter One Hospital
- CCOP - Dayton
- CCOP - Toledo Community Hospital
- CCOP - Upstate Carolina
- Rapid City Regional Hospital
- CCOP - Sioux Community Cancer Consortium
- CCOP - St. Vincent Hospital Cancer Center, Green Bay
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Arm I - lamotrigine
Arm II - placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT00068445
First Posted
September 10, 2003
Last Updated
April 3, 2018
Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00068445
Brief Title
Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
Official Title
The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
November 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurotoxicity, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
neurotoxicity, pain, unspecified adult solid tumor, protocol specific
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
131 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I - lamotrigine
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II - placebo
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
lamotrigine
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS)
Description
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.
Time Frame
From baseline to week 10
Title
Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS)
Description
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.
Time Frame
From baseline to week 10
Secondary Outcome Measure Information:
Title
The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10
Description
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.
Time Frame
From baseline to week 10
Title
Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline]
Description
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.
Time Frame
From baseline to week 10
Title
Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline]
Description
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
Time Frame
From baseline to week 10
Title
Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline]
Description
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.
Time Frame
From baseline to week 10
Title
Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline]
Description
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.
Time Frame
From baseline to week 10
Title
Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline]
Description
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.
Time Frame
From baseline to week 10
Title
Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline]
Description
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.
Time Frame
From baseline to week 10
Title
Change in POMS Total Score [Week 10 Minus Baseline]
Description
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.
Time Frame
From baseline to week 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ravi D. Rao, MD, MBBS
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Mayo Clinic - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
CCOP - Atlanta Regional
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342-1701
Country
United States
Facility Name
MBCCOP - Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
CCOP - Illinois Oncology Research Association
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615-7828
Country
United States
Facility Name
CCOP - Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
CCOP - Cedar Rapids Oncology Project
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52403-1206
Country
United States
Facility Name
CCOP - Iowa Oncology Research Association
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309-1854
Country
United States
Facility Name
Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101-1733
Country
United States
Facility Name
CCOP - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214-3882
Country
United States
Facility Name
CCOP - Michigan Cancer Research Consortium
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
CCOP - Duluth
City
Duluth
State/Province
Minnesota
ZIP/Postal Code
55805
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Coborn Cancer Center
City
Saint Cloud
State/Province
Minnesota
ZIP/Postal Code
56303
Country
United States
Facility Name
CCOP - Metro-Minnesota
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
CCOP - Missouri Valley Cancer Consortium
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68106
Country
United States
Facility Name
Cancer Care Center at Medcenter One Hospital
City
Bismarck
State/Province
North Dakota
ZIP/Postal Code
58501-5505
Country
United States
Facility Name
CCOP - Dayton
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
CCOP - Toledo Community Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623-3456
Country
United States
Facility Name
CCOP - Upstate Carolina
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Rapid City Regional Hospital
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57709
Country
United States
Facility Name
CCOP - Sioux Community Cancer Consortium
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57104
Country
United States
Facility Name
CCOP - St. Vincent Hospital Cancer Center, Green Bay
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
18428211
Citation
Rao RD, Flynn PJ, Sloan JA, Wong GY, Novotny P, Johnson DB, Gross HM, Renno SI, Nashawaty M, Loprinzi CL. Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3. Cancer. 2008 Jun 15;112(12):2802-8. doi: 10.1002/cncr.23482.
Results Reference
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Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
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