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Lamotrigine during 28 consecutive weeks:

* 8 weeks dose-increase phase: from 25mg once daily to 100mg twice daily
* 18 weeks target-dose phase: 100mg twice daily
* 2 weeks decline-phase: 100mg once daily.

Placebo tablets during 28 consecutive weeks, with identical appearance to lamotrigine tablets, mimicking the lamotrigine dosing schedule.

Placebo

Ype Elgersma, PhD

Henriette A Moll, MD, PhD

The purpose of this study is to determine whether lamotrigine can improve cognitive and neurophysiological deficits in adolescents with Neurofibromatosis type 1.

Cognitive deficits in the autosomal dominant disorder Neurofibromatosis type 1 (NF1) typically consist of a lower than average IQ, impaired visual-spatial learning, attention problems and impaired executive functioning. These deficits have a substantial influence on the daily life of pediatric and adolescent individuals with NF1. One of the key underlying mechanisms of these deficits is an increased gamma-aminobutyric acid (GABA)-ergic inhibition and a subsequent decrease in synaptic plasticity. The ENCORE laboratory has recently shown that loss of the NF1-gene is associated with attenuated function of the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1). These channels, enriched in membranes of inhibitory interneurons, play an important role in the pathophysiology underlying the cognitive deficits in NF1. Lamotrigine, an HCN-agonist, restored function of HCN1, together with the electrophysiological and visual-spatial learning deficits in Nf1-mice. Thus, lamotrigine is a novel candidate drug for treating cognitive deficits associated with NF1.

Effect of Lamotrigine on Cognition in NF1

The Effect of Lamotrigine on Cognitive Deficits Associated With Neurofibromatosis Type 1: a Phase II Randomized Controlled Multi-centre Trial (NF1-EXCEL)

Assessed by the Wechsler Intelligence Scales for children - third edition (WISC-III).

Pharmacokinetic model build with NONMEM analysis of trough level, Tmax level and a level 6 hours post-dose.

Determined by highest educational grade as measured with the "Standaard Onderwijsindeling (SOI)" classification by Statistics Netherlands (Centraal Bureau voor Statistiek; CBS)

Determined by the most appropriate level of education for the particular occupation

Determined using the ISCED (International Standard Classification of Education) 2011 levels

Assessed by the Wechsler Intelligence Scales for Children - third edition (WISC-III).

Assessed by the Paired Associative Learning (PAL) task of the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Assessed by the Motor Free Visual Perception Test - third edition (MVPT-3).

Assessed by the Sustained Attention DOTS (SA-DOTS) of the Amsterdam Neuropsychological Tasks (ANT).

Assessed by the Beery-Buktenica Developmental Task of Visual Motor Integration - sixth edition (Beery-VMI-6).

Assessed by a parent rated ADHD-questionnaire, the ADHD-vragenlijst (AVL).

Assessed by the Behavior Rating Inventory for Executive Function parent questionnaire (BRIEF).

Assessed by paired pulse transcranial magnetic stimulation (ppTMS).

Assessed by paired associative stimulation (PAS) using transcranial magnetic stimulation (TMS).

Universitaire Ziekenhuizen KU Leuven

ZonMw: The Netherlands Organisation for Health Research and Development

Hospital Sant Joan de Deu

Erasmus Medical Center

MD, MSc

Substance Related Disorders

Pain

Neurotoxicity Syndromes

Poisoning

Chemically-Induced Disorders

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.

lamotrigine

Ravi D. Rao, MD, MBBS

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.

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.

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

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

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.

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.

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.

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.

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

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.

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 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.

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.

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.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Each CTCAE term is a unique representation of a specific event used for medical documentation/scientific analysis and is a single MedDRA Lowest Level Term (LLT). All AEs are reported below for patients who reported AEs for cycle \>0 and grade \>0.Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and appear in the SAE table.

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.

Arm I - Lamotrigine

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.

Arm II - Placebo

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Charles L. Loprinzi, M.D.

Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS)

Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS)

Participants with Uniscale QOL data at both time points available were assessed.

The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10

Participants with BPI Worst Pain data at both time points available were assessed.

Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline]

Participants with BPI Least Pain data at both time points available were assessed.

Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline]

Participants with BPI Average Pain data at both time points available were assessed.

Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline]

Participants with BPI Pain Now data at both time points available were assessed.

Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline]

Participants with BPI Pain Relief data at both time points available were assessed.

Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline]

Participants with BPI Pain Interference data at both time points available were assessed.

Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline]

Participants with POMS scales data at both time points available were assessed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Effect of Lamotrigine on Cognition in NF1	NCT02256124	Neurofibromatos...	Lamotrigine Placebo	12 Years - 18 Years	Erasmus Medical Center
Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer	NCT00068445	Neurotoxicity Pain Unspecified Adu...	lamotrigine Placebo	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for lamotrigine

Every month we try and update this database with for lamotrigine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lamotrigine

Every month we try and update this database with for lamotrigine cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lamotrigine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.