NeurotoxicityPhase 3NCT00068445
Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
A Phase 3 study testing lamotrigine in people with Neurotoxicity and Pain, run by Alliance for Clinical Trials in Oncology at 23 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurotoxicity, Pain, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- lamotrigine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 131 participants
- Where
- 23 sitesUnited States
- Study dates
- Feb 2004to Nov 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, 48106
CCOP - Atlanta Regional
Atlanta, Georgia, 30342-1701
Cancer Care Center at Medcenter One Hospital
Bismarck, North Dakota, 58501-5505
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, 52403-1206
CCOP - Dayton
Dayton, Ohio, 45429
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, 50309-1854
CCOP - Duluth
Duluth, Minnesota, 55805
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, 54301
MBCCOP - Hawaii
Honolulu, Hawaii, 96813
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106
CCOP - Illinois Oncology Research Association
Peoria, Illinois, 61615-7828
Rapid City Regional Hospital
Rapid City, South Dakota, 57709
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Coborn Cancer Center
Saint Cloud, Minnesota, 56303
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259
Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center
Sioux City, Iowa, 51101-1733
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, 57104
CCOP - Upstate Carolina
Spartanburg, South Carolina, 29303
CCOP - Toledo Community Hospital
Toledo, Ohio, 43623-3456
CCOP - Carle Cancer Center
Urbana, Illinois, 61801
CCOP - Wichita
Wichita, Kansas, 67214-3882
About this study
Official title: The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
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.
Read the 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.
- Being tested
- lamotrigine, Placebo
- Keywords
- neurotoxicity, pain, unspecified adult solid tumor, protocol specific
- Medical subject headings
- Neurotoxicity Syndromes, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lamotrigineDrug
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Arm I - lamotrigine | Experimental | 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. Receives: Drug: lamotrigine |
| Arm II - placebo | Other | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From baseline to week 10
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From baseline to week 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2003 (estimated)
- Study startFeb 2004
- Primary completionMay 2006
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeurotoxicityStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ravi D. Rao, MD, MBBS, Study chair, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00068445
- Sponsor's protocol ID
- NCCTG-N01C3
- Other IDs
- CDR0000322830
- Status last verified
- Apr 2018
- First submitted
- 10 Sep 2003
- Last updated
- 4 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 18428211
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT00068445
- Acronym / sponsor ID
- NCCTG-N01C3
- Keywords
- neurotoxicity, pain, unspecified adult solid tumor, protocol specific
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2004
- Primary completion
- May 2006 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 11 Sep 2003 (estimated)
- Results
- Posted 4 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I - lamotrigine | Experimental | Drug: lamotriginePatients 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 II - placebo | Other | Other: PlaceboPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lamotrigine | Drug | Arm I - lamotrigine |
| Placebo | Other | Arm II - placebo |
Primary outcome
Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS)
Time frame: 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)
Time frame: 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.
8 secondary outcomes
The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10
Time frame: From baseline to week 10
Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline]
Time frame: From baseline to week 10
Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline]
Time frame: From baseline to week 10
Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline]
Time frame: From baseline to week 10
Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline]
Time frame: From baseline to week 10
Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline]
Time frame: From baseline to week 10
Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline]
Time frame: From baseline to week 10
Change in POMS Total Score [Week 10 Minus Baseline]
Time frame: From baseline to week 10
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 18428211Rao 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi D. Rao, MD, MBBS study chair
Mayo Clinic
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing lamotrigine in people with Neurotoxicity and Pain, run by Alliance for Clinical Trials in Oncology at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS) (time frame: From baseline to week 10). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00068445, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2018.