Recruiting

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

ClinicalTrials.gov IDNCT07633626

PhaseNot Applicable

Enrollment24

SponsorCentro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo

Age18 Years

SexALL

I'm interested View official listing

Conditions studied

Advanced ALK/ROS1-positive NSCLC, Carcinoma, Non-Small-Cell Lung (NSCLC), Lung Adenocarcinoma, ALK-positive Non-small Cell Lung Cancer (NSCLC), Cognitive Dysfunction, Depression

About this study

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.

Primary outcomes

Psychomotor Speed (Baseline, Week 6, Week 12)
Processing Speed and Visual Attention (Baseline, Week 6, Week 12)
Executive Function and Cognitive Flexibility (Baseline, Week 6, Week 12)
Selective and Sustained Attention (Baseline, Week 6, Week 12)
Working Memory (Baseline, Week 6, Week 12)
Processing Speed (Baseline, Week 6, Week 12)
Verbal Learning and Memory (Baseline, Week 6, Week 12)
Language (Baseline, Week 6, Week 12)

Eligibility information

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Study locations

Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo CTIC, Bogotá, 110131 Colombia

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.