Neurotoxicity, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
neurotoxicity, pain, unspecified adult solid tumor, protocol specific
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.
Interventions
DRUGlamotrigine
OTHERPlacebo
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS) | From baseline to week 10 | 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) | From baseline to week 10 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline] | From baseline to week 10 | 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] | From baseline to week 10 | 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] | From baseline to week 10 | 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. |
| The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10 | 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) Pain Interference Score [Week 10 Minus Baseline] | From baseline to week 10 | 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] | From baseline to week 10 | 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. |
| Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline] | From baseline to week 10 | 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) Worst Pain Score [Week 10 Minus Baseline] | From baseline to week 10 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I - Lamotrigine Patients receive oral lamotrigine (25 mg per pill) once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. | 63 |
| Arm II - Placebo Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. | 62 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization | Cancel | 1 | 3 |
| Randomization | Ineligible | 1 | 1 |
| Treatment | Adverse Event | 7 | 1 |
| Treatment | Other (Specifics not available) | 9 | 5 |
| Treatment | Refused Further Treatment | 13 | 10 |
Baseline characteristics
| Characteristic | Arm I - Lamotrigine | Arm II - Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 59 years | 61 years |
| Region of Enrollment United States | 63 Participants | 62 Participants | 125 Participants |
| Sex: Female, Male Female | 36 Participants | 38 Participants | 74 Participants |
| Sex: Female, Male Male | 27 Participants | 24 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 63 |
| other Total, other adverse events | 26 / 61 | 24 / 63 |
| serious Total, serious adverse events | 0 / 61 | 0 / 63 |
Outcome results
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.
Time frame: From baseline to week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS) | -0.3 units on a scale | Standard Deviation 2.76 |
| Arm II - Placebo | Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS) | -0.5 units on a scale | Standard Deviation 2.34 |
p-value: 0.56Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS) | -0.4 units on a scale | Standard Deviation 0.73 |
| Arm II - Placebo | Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS) | -0.3 units on a scale | Standard Deviation 1 |
p-value: 0.36Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
Population: Participants with BPI Average Pain data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline] | -0.1 units on a scale | Standard Deviation 2.15 |
| Arm II - Placebo | Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline] | -0.8 units on a scale | Standard Deviation 2.35 |
p-value: 0.22Wilcoxon (Mann-Whitney)
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
Time frame: From baseline to week 10
Population: Participants with BPI Least Pain data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline] | 0.2 units on a scale | Standard Deviation 2.12 |
| Arm II - Placebo | Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline] | 0.1 units on a scale | Standard Deviation 1.97 |
p-value: 0.53Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
Population: Participants with BPI Pain Interference data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline] | -0.5 units on a scale | Standard Deviation 2.17 |
| Arm II - Placebo | Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline] | -0.8 units on a scale | Standard Deviation 2.19 |
p-value: 0.91Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
Population: Participants with BPI Pain Now data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline] | -0.1 units on a scale | Standard Deviation 2.77 |
| Arm II - Placebo | Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline] | -0.3 units on a scale | Standard Deviation 2.22 |
p-value: 0.33Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
Population: Participants with BPI Pain Relief data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline] | 6.7 units on a scale | Standard Deviation 28.34 |
| Arm II - Placebo | Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline] | 0.4 units on a scale | Standard Deviation 30.34 |
p-value: 0.07Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
Population: Participants with BPI Worst Pain data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline] | 0.1 units on a scale | Standard Deviation 3.17 |
| Arm II - Placebo | Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline] | -0.6 units on a scale | Standard Deviation 2.31 |
p-value: 0.34Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
Population: Participants with POMS scales data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | Change in POMS Total Score [Week 10 Minus Baseline] | 1.4 units on a scale | Standard Deviation 10.67 |
| Arm II - Placebo | Change in POMS Total Score [Week 10 Minus Baseline] | 1.3 units on a scale | Standard Deviation 9.09 |
p-value: 0.68Wilcoxon (Mann-Whitney)
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.
Time frame: From baseline to week 10
Population: Participants with Uniscale QOL data at both time points available were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Lamotrigine | The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10 | -4.3 units on a scale | Standard Deviation 25.15 |
| Arm II - Placebo | The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10 | 0.3 units on a scale | Standard Deviation 22.09 |
p-value: 0.25Wilcoxon (Mann-Whitney)