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

June 4, 2026 updated by: Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo

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

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.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

24

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adults (>= 18 years) with histologically confirmed advanced (stage IIIB/IV) lung adenocarcinoma harboring ALK or ROS1 fusions, currently receiving lorlatinib as standard care, and initiating vortioxetine for NAE management.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Psychomotor Speed
Time Frame: Baseline, Week 6, Week 12
Digit Symbol Substitution Test (DSST). The DSST measures psychomotor speed and sustained attention. Participants match symbols to digits within a fixed time limit. Score range: 0 to 90 (number of correct substitutions in 90 seconds); higher scores indicate better cognitive performance. Within-subject change from baseline analyzed using ANCOVA.
Baseline, Week 6, Week 12
Processing Speed and Visual Attention
Time Frame: Baseline, Week 6, Week 12
Trail Making Test Part A (TMT-A). The TMT-A measures processing speed and visual scanning. The outcome is time to completion in seconds; lower scores indicate better performance. Clinically meaningful change assessed using the Reliable Change Index (RCI).
Baseline, Week 6, Week 12
Executive Function and Cognitive Flexibility
Time Frame: Baseline, Week 6, Week 12
Trail Making Test Part B (TMT-B). The TMT-B measures executive function and set-shifting ability. The outcome is time to completion in seconds; lower scores indicate better performance. Clinically meaningful change assessed using the Reliable Change Index (RCI).
Baseline, Week 6, Week 12
Selective and Sustained Attention
Time Frame: Baseline, Week 6, Week 12
D2-R Test of Attention. The D2-R Test of Attention measures selective and sustained visual attention. The primary metric is the Total Concentration Performance score (TN-E), calculated as total items processed minus errors. Score range: 0 to 299; higher scores indicate better attentional performance.
Baseline, Week 6, Week 12
Working Memory
Time Frame: Baseline, Week 6, Week 12
Wechsler Adult Intelligence Scale IV (WAIS-IV), Working Memory Index. The WAIS-IV Working Memory Index is a standardized composite score derived from Digit Span and Arithmetic subtests. Score range: 45 to 155 (mean 100, SD 15); higher scores indicate better working memory capacity. Change from baseline analyzed using linear mixed-effects models (LMM).
Baseline, Week 6, Week 12
Processing Speed
Time Frame: Baseline, Week 6, Week 12
Wechsler Adult Intelligence Scale IV (WAIS-IV), Processing Speed Index. The WAIS-IV Processing Speed Index is a standardized composite score derived from Coding and Symbol Search subtests. Score range: 45 to 155 (mean 100, SD 15); higher scores indicate better processing speed. Change from baseline analyzed using LMM.
Baseline, Week 6, Week 12
Verbal Learning and Memory
Time Frame: Baseline, Week 6, Week 12
California Verbal Learning Test (CVLT). The California Verbal Learning Test measures verbal learning and episodic memory across five immediate recall trials plus short- and long-delay recall. Primary metric: Total Learning Trials 1-5 (score range: 0 to 80); higher scores indicate better verbal memory performance.
Baseline, Week 6, Week 12
Language
Time Frame: Baseline, Week 6, Week 12
Phonemic Verbal Fluency Task. Phonemic verbal fluency is measured by the total number of words beginning with a specified letter generated in 60 seconds. There is no fixed maximum; higher scores indicate better phonemic language production and frontal-executive function. The average of three letter trials (F, A, S) will be reported.
Baseline, Week 6, Week 12
Language
Time Frame: Baseline, Week 6, Week 12
Semantic Verbal Fluency Task. Semantic verbal fluency is measured by the total number of words from a specified semantic category generated in 60 seconds. There is no fixed maximum; higher scores indicate better semantic retrieval and language functioning.
Baseline, Week 6, Week 12
Frontal Lobe and Executive Function
Time Frame: Baseline, Week 6, Week 12
INECO Frontal Screening (IFS). The INECO Frontal Screening (IFS) evaluates frontal lobe functions including motor programming, verbal fluency inhibitory control, working memory, abstraction capacity, and reflex suppression. Score range: 0 to 30; higher scores indicate better executive and frontal lobe functioning.
Baseline, Week 6, Week 12
Subjective Cognitive Complaints
Time Frame: Baseline, Week 6, Week 12
Perceived Deficits Questionnaire (PDQ), Attention/Concentration Subscore. The PDQ Attention/Concentration subscore measures self-reported cognitive difficulties in attention and concentration. Subscore range: 0 to 20; higher scores indicate greater perceived cognitive impairment. Analyzed using mixed models for repeated measures (MMRM).
Baseline, Week 6, Week 12
Subjective Cognitive Complaints
Time Frame: Baseline, Week 6, Week 12
Perceived Deficits Questionnaire (PDQ), Planning/Organization Subscore. The PDQ Planning/Organization subscore measures self-reported difficulties in planning and organizational ability. Subscore range: 0 to 20; higher scores indicate greater perceived impairment. Analyzed using MMRM.
Baseline, Week 6, Week 12
Clinical Global Impression of Improvement (CGI-I)
Time Frame: Baseline, Week 6, Week 12
The Clinical Global Impressions-Improvement scale (CGI-I) is a clinician-rated measure of overall clinical improvement relative to baseline. Score range: 1 (very much improved) to 7 (very much worse); lower scores indicate greater improvement. Response is defined as a score of 1 or 2. Analyzed using MMRM.
Baseline, Week 6, Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Depressive Symptoms
Time Frame: Baseline, Week 6, Week 12, Month 6
Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is a clinician-administered scale measuring severity of depressive symptoms across 10 items. Score range: 0 to 60; higher scores indicate greater depression severity. Response defined as >= 50% reduction from baseline; remission defined as score < 10. MCID: >= 50% reduction.
Baseline, Week 6, Week 12, Month 6
Depressive Symptoms
Time Frame: Baseline, Week 6, Week 12
Patient Health Questionnaire (PHQ-9). The PHQ-9 is a 9-item self-report scale for depression screening and severity assessment. Score range: 0 to 27; higher scores indicate greater depressive symptom burden. Severity categories: minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). MCID: >= 5-point reduction.
Baseline, Week 6, Week 12
Health-Related Quality of Life
Time Frame: Baseline, Month 1, 2, 3, 6, 12
36-Item Short Form Health Survey (SF-36), Physical Component Summary (PCS). The SF-36 Physical Component Summary (PCS) is a norm-based composite score derived from four SF-36 subscales (physical functioning, role-physical, bodily pain, general health). Score range: 0 to 100; higher scores indicate better physical health status. MCID: >= 4 points.
Baseline, Month 1, 2, 3, 6, 12
Health-Related Quality of Life
Time Frame: Baseline, Month 1, 2, 3, 6, 12
36-Item Short Form Health Survey (SF-36), Mental Component Summary (MCS). The SF-36 Mental Component Summary (MCS) is a norm-based composite score derived from four SF-36 subscales (vitality, social functioning, role-emotional, mental health). Score range: 0 to 100; higher scores indicate better mental health status. MCID: >= 4 points.
Baseline, Month 1, 2, 3, 6, 12
Life Satisfaction
Time Frame: Baseline, Month 1, 2, 3, 6, 12
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). The Q-LES-Q-SF measures overall enjoyment and satisfaction with daily life across 14 items rated on a 5-point Likert scale (1 = very poor to 5 = very good). Total score range: 14 to 70; higher scores indicate greater life satisfaction. Items 15 and 16 are scored separately and not included in the total. MCID: >= 9 points.
Baseline, Month 1, 2, 3, 6, 12
Health Utility
Time Frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
EuroQol 5-Dimension Questionnaire (EQ-5D), Utility Index. The EQ-5D utility index is derived from five health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) using the Spanish value set. Score range: -0.654 to 1.0; higher scores indicate better health utility (1.0 = full health, 0 = death). MCID: >= 0.1.
Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
Self-Rated Health
Time Frame: Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
EuroQol Visual Analogue Scale (EQ-VAS). The EQ-VAS is a vertical visual analogue scale for overall self-rated health. Score range: 0 to 100; higher scores indicate better self-rated health (100 = best imaginable health state). MCID: >= 7 points.
Baseline, Month 1, Month 2, Month 3, Month 6, Month 12
Functional Capacity
Time Frame: Baseline, Week 6, Week 12
University of California San Diego Performance-Based Skills Assessment (UPSA), Composite Score. The UPSA composite score combines the UPSA-VIM and UPSA-Brief to measure real-world functional capacity across domains including finance and communication. Score range: 0 to 100; higher scores indicate better functional performance. Analyzed using ANCOVA.
Baseline, Week 6, Week 12
Work Limitations
Time Frame: Baseline, Week 6, Week 12, Month 6
Work Limitations Questionnaire (WLQ). The WLQ measures the degree to which health problems interfere with job performance across four scales: time management, physical demands, mental-interpersonal demands, and output demands. Each scale is scored 0 to 100; higher scores indicate greater work limitation. An overall WLQ productivity loss score will also be reported.
Baseline, Week 6, Week 12, Month 6
Cognitive and Physical Functioning
Time Frame: Baseline, Week 6, Week 12
Cognitive and Physical Functioning Questionnaire (CPFQ). The CPFQ is a 7-item self-report instrument measuring cognitive and physical energy symptoms relevant to depression and related conditions. Score range: 7 to 42; higher scores indicate greater cognitive and physical impairment. Analyzed only in participants with a baseline score > 25.
Baseline, Week 6, Week 12
Tumor Response to Lorlatinib
Time Frame: Month 2, Month 6, Month 12
Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Tumor response is assessed by contrast-enhanced CT scan per RECIST version 1.1 criteria. Response is classified as: Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). Best overall response will be documented for each participant.
Month 2, Month 6, Month 12
Adverse Events
Time Frame: All scheduled visits, from baseline through 30 days post-last visit
Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. All adverse events (AEs) will be graded by type, severity (Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening; Grade 5: death), and causality attribution (unrelated / unlikely / possible / probable / definitely related to vortioxetine). Predefined study suspension thresholds: > 25% Grade 3, > 10% Grade 4, or > 3% Grade 5 AEs attributable to vortioxetine.
All scheduled visits, from baseline through 30 days post-last visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2026

Primary Completion (Estimated)

March 10, 2027

Study Completion (Estimated)

November 10, 2027

Study Registration Dates

First Submitted

April 14, 2026

First Submitted That Met QC Criteria

June 4, 2026

First Posted (Actual)

June 8, 2026

Study Record Updates

Last Update Posted (Actual)

June 8, 2026

Last Update Submitted That Met QC Criteria

June 4, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Vortioxetina

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Depression

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe