Vortioxetine for Cognitive Function in ALK-positive NSCLC Treated With Lorlatinib

Официальное название

Potential Effect of Vortioxetine on Cognitive Functioning of Patients With ALK-positive Non-Small Cell Lung Cancer Treated With Lorlatinib

Обзор

This observational study evaluates whether vortioxetine - an antidepressant medication with cognitive-enhancing properties - can reduce the neurological and cognitive side effects associated with lorlatinib treatment in patients with non-small cell lung cancer (NSCLC) harboring ALK or ROS1 gene rearrangements. Lorlatinib is a highly effective third-generation tyrosine kinase inhibitor, but it causes neuropsychological adverse events (NAEs) in approximately 42% of patients, including cognitive impairment, mood changes, and speech disturbances. Vortioxetine has demonstrated cognitive improvement in depressed patients and in preclinical models of androgen deprivation therapy-induced cognitive impairment. Twenty-four adult patients with ALK/ROS1-positive NSCLC receiving lorlatinib as standard care and prescribed vortioxetine (10-20 mg/day) for NAE management will be enrolled. Comprehensive neuropsychological assessments and quality-of-life questionnaires will be conducted at baseline, week 6, week 12, and month 6 to document changes in cognitive function, depressive symptoms, and quality of life.

Первичные конечные точки

• Psychomotor Speed [Срок оценки: Baseline, Week 6, Week 12]
• Processing Speed and Visual Attention [Срок оценки: Baseline, Week 6, Week 12]
• Executive Function and Cognitive Flexibility [Срок оценки: Baseline, Week 6, Week 12]
• Selective and Sustained Attention [Срок оценки: Baseline, Week 6, Week 12]
• Working Memory [Срок оценки: Baseline, Week 6, Week 12]
• Processing Speed [Срок оценки: Baseline, Week 6, Week 12]
• Verbal Learning and Memory [Срок оценки: Baseline, Week 6, Week 12]
• Language [Срок оценки: Baseline, Week 6, Week 12]
• Language [Срок оценки: Baseline, Week 6, Week 12]
• Frontal Lobe and Executive Function [Срок оценки: Baseline, Week 6, Week 12]

Вторичные конечные точки (12)

• Depressive Symptoms [Срок оценки: Baseline, Week 6, Week 12, Month 6]
• Depressive Symptoms [Срок оценки: Baseline, Week 6, Week 12]
• Health-Related Quality of Life [Срок оценки: Baseline, Month 1, 2, 3, 6, 12]
• Health-Related Quality of Life [Срок оценки: Baseline, Month 1, 2, 3, 6, 12]
• Life Satisfaction [Срок оценки: Baseline, Month 1, 2, 3, 6, 12]
• Health Utility [Срок оценки: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12]
• Self-Rated Health [Срок оценки: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12]
• Functional Capacity [Срок оценки: Baseline, Week 6, Week 12]
• Work Limitations [Срок оценки: Baseline, Week 6, Week 12, Month 6]
• Cognitive and Physical Functioning [Срок оценки: Baseline, Week 6, Week 12]
• Tumor Response to Lorlatinib [Срок оценки: Month 2, Month 6, Month 12]
• Adverse Events [Срок оценки: All scheduled visits, from baseline through 30 days post-last visit]

Критерии участия

Критерии включения

• Histologically confirmed diagnosis of ALK/ROS1-positive non-small cell lung cancer (NSCLC), stage IIIB/IV.
• Currently receiving lorlatinib as part of the standard therapeutic regimen.
• Documented neurocognitive adverse events (NAEs) attributable to lorlatinib.
• Age >= 18 years.
• ECOG performance status 0-2.
• Ability to understand and sign informed consent.
• Expected survival >= 6 months.
• Planned initiation of vortioxetine as part of standard care.
• Ability to complete neuropsychological tests and questionnaires in Spanish.

Критерии исключения

• Prior diagnosis of major cognitive impairment unrelated to cancer treatment.
• Current use of another antidepressant that cannot be discontinued.
• Uncontrolled major psychiatric disorder.
• History of uncontrolled epilepsy or recent seizures.
• Severe hepatic or renal impairment.
• Known hypersensitivity to vortioxetine.
• Participation in another clinical trial within the past 30 days.
• Inability to provide informed consent.
• Life expectancy < 3 months.
• Contraindications to vortioxetine (e.g., concomitant MAOI use).
• Prior vortioxetine use.
• Severe psychiatric disorders or significant cognitive impairment unrelated to lorlatinib.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Только случаи

Центры проведения

Колумбия · 1 центр

• Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo CTIC — Bogotá

Публикации

• Sharp AM, Lertphinyowong S, Yee SS, Paredes D, Gelfond J, Johnson-Pais TL, Leach RJ, Liss M, Risinger AL, Sullivan AC, Thompson IM, Morilak DA. Vortioxetine reverses medial prefrontal cortex-mediated cognitive deficits in male rats induced by castration as a model of androgen deprivation therapy for prostate cancer. Psychopharmacology (Berl). 2019 Nov;236(11):3183-3195. doi: 10.1007/s00213-019-052 PMID 31139875
• Vaiana AM, Chen Y, Gelfond J, Johnson-Pais TL, Leach RJ, Ramamurthy C, Thompson IM, Morilak DA. Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment. Transl Psychiatry. 2023 Oct 3;13(1):307. doi: 10.1038/s41398-023-02600-5. PMID 37788996
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• He D, Lasek AW. Anaplastic Lymphoma Kinase Regulates Internalization of the Dopamine D2 Receptor. Mol Pharmacol. 2020 Feb;97(2):123-131. doi: 10.1124/mol.119.117473. Epub 2019 Nov 16. PMID 31734646
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Идентификаторы

NCT: NCT07633626 · Vortioxetina

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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