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

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ClinicalTrials.gov Identifier: NCT00068445
Recruitment Status : Completed
First Posted : September 11, 2003
Results First Posted : May 4, 2018
Last Update Posted : May 4, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

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.


Condition or disease Intervention/treatment Phase
Neurotoxicity Pain Unspecified Adult Solid Tumor, Protocol Specific Drug: lamotrigine Other: Placebo Phase 3

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
Study Start Date : February 2004
Actual Primary Completion Date : May 2006
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Lamotrigine

Arm Intervention/treatment
Experimental: Arm I - lamotrigine

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
Arm II - placebo

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



Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline] [ Time Frame: 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.

  3. Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline] [ Time Frame: 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


  4. Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline] [ Time Frame: 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.

  5. Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline] [ Time Frame: 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.

  6. Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline] [ Time Frame: 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.

  7. Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline] [ Time Frame: 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.

  8. Change in POMS Total Score [Week 10 Minus Baseline] [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00068445


  Show 23 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Ravi D. Rao, MD, MBBS Mayo Clinic

Publications of Results:
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, 475s, 2006.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00068445     History of Changes
Other Study ID Numbers: NCCTG-N01C3
CDR0000322830 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: September 11, 2003    Key Record Dates
Results First Posted: May 4, 2018
Last Update Posted: May 4, 2018
Last Verified: April 2018

Keywords provided by Alliance for Clinical Trials in Oncology:
neurotoxicity
pain
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Peripheral Nervous System Diseases
Neurotoxicity Syndromes
Neuromuscular Diseases
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Lamotrigine
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers