Advanced ALK/ROS1-positive NSCLCNCT07633626

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

An observational study of Advanced ALK/ROS1-positive NSCLC and Carcinoma, Non-Small-Cell Lung (NSCLC), run by Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo at 1 site in Colombia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced ALK/ROS1-positive NSCLC, Carcinoma, Non-Small-Cell Lung (NSCLC), Lung Adenocarcinoma
How many people: 24 participants
Where: 1 siteColombia
Study dates: 10 Mar 2026to 10 Nov 2027
Phase: Observational

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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.

Who may be able to join

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.

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Expected survival >= 6 months.
Planned initiation of vortioxetine as part of standard care.
Ability to complete neuropsychological tests and questionnaires in Spanish.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Felipe Canro, MD contact

+57 310 8593083

felipe.canro@gmail.com

Colombia1 site, 1 recruiting

Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo CTIC
Bogotá, 110131
LIliana Gutierrez, RN, MSc, +573003768158, lgutierrez@fctic.org
Recruiting

Other trials in Colombia

About this study

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

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.

Conditions: Advanced ALK/ROS1-positive NSCLC, Carcinoma, Non-Small-Cell Lung (NSCLC), Lung Adenocarcinoma, ALK-positive Non-small Cell Lung Cancer (NSCLC), Cognitive Dysfunction, Depression
Medical subject headings: Carcinoma, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma of Lung, Cognitive Dysfunction, Depression

What is being measured

The primary outcome is the main question the study is designed to answer.

Psychomotor Speed
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.
Measured: Baseline, Week 6, Week 12
Processing Speed and Visual Attention
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).
Measured: Baseline, Week 6, Week 12
Executive Function and Cognitive Flexibility
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).
Measured: Baseline, Week 6, Week 12
Selective and Sustained Attention
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.
Measured: Baseline, Week 6, Week 12
Working Memory
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).
Measured: Baseline, Week 6, Week 12
Processing Speed
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.
Measured: Baseline, Week 6, Week 12
Verbal Learning and Memory
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.
Measured: Baseline, Week 6, Week 12
Language
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.
Measured: Baseline, Week 6, Week 12
Language
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.
Measured: Baseline, Week 6, Week 12
Frontal Lobe and Executive Function
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.
Measured: Baseline, Week 6, Week 12
Subjective Cognitive Complaints
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).
Measured: Baseline, Week 6, Week 12
Subjective Cognitive Complaints
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.
Measured: Baseline, Week 6, Week 12
Clinical Global Impression of Improvement (CGI-I)
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.
Measured: Baseline, Week 6, Week 12

Secondary outcomes (12)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Mar 202610 Nov 2027

First posted8 Jun 2026
Study start10 Mar 2026
Primary completion10 Mar 2027 (estimated)
Study completion10 Nov 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (36)Papers the sponsor has linked to this study.
Other trials for Advanced ALK/ROS1-positive NSCLCStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case only
Time perspective: Prospective
Enrolment: 24 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07633626
Sponsor's protocol ID: Vortioxetina
Status last verified: Jun 2026
First submitted: 14 Apr 2026
Last updated: 8 Jun 2026
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

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/s00213-019-05274-4. Epub 2019 May 28.
PubMed 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.
PubMed 37788996
Chen G, Hojer AM, Areberg J, Nomikos G. Vortioxetine: Clinical Pharmacokinetics and Drug Interactions. Clin Pharmacokinet. 2018 Jun;57(6):673-686. doi: 10.1007/s40262-017-0612-7.
PubMed 29189941
Mork A, Pehrson A, Brennum LT, Nielsen SM, Zhong H, Lassen AB, Miller S, Westrich L, Boyle NJ, Sanchez C, Fischer CW, Liebenberg N, Wegener G, Bundgaard C, Hogg S, Bang-Andersen B, Stensbol TB. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther. 2012 Mar;340(3):666-75. doi: 10.1124/jpet.111.189068. Epub 2011 Dec 9.
PubMed 22171087
Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12.
PubMed 21486038
Kugathasan P, Waller J, Westrich L, Abdourahman A, Tamm JA, Pehrson AL, Dale E, Gulinello M, Sanchez C, Li Y. In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity. J Psychopharmacol. 2017 Mar;31(3):365-376. doi: 10.1177/0269881116667710. Epub 2016 Sep 28.
PubMed 27678087
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.
PubMed 31734646
Dutton JW 3rd, Chen H, You C, Brodie MS, Lasek AW. Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area. Addict Biol. 2017 May;22(3):665-678. doi: 10.1111/adb.12358. Epub 2016 Jan 11.
PubMed 26752591
Sisi M, Fusaroli M, De Giglio A, Facchinetti F, Ardizzoni A, Raschi E, Gelsomino F. Psychiatric Adverse Reactions to Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer: Analysis of Spontaneous Reports Submitted to the FDA Adverse Event Reporting System. Target Oncol. 2022 Jan;17(1):43-51. doi: 10.1007/s11523-021-00865-8. Epub 2022 Jan 13.
PubMed 35025076
Dagogo-Jack I, Oxnard GR, Evangelist M, Digumarthy SR, Lin JJ, Gainor JF, Murphy JF, Rabin MS, Heist RS, Muzikansky A, Shaw AT. Phase II Study of Lorlatinib in Patients With Anaplastic Lymphoma Kinase-Positive Lung Cancer and CNS-Specific Relapse. JCO Precis Oncol. 2022 May;6:e2100522. doi: 10.1200/PO.21.00522.
PubMed 35584349
Jia K, Ren S. Neurocognitive Adverse Events of Lorlatinib: On the Way to Precise Prediction? J Thorac Oncol. 2023 Jan;18(1):26-28. doi: 10.1016/j.jtho.2022.11.003. No abstract available.
PubMed 36543433
Bauer TM, Felip E, Solomon BJ, Thurm H, Peltz G, Chioda MD, Shaw AT. Clinical Management of Adverse Events Associated with Lorlatinib. Oncologist. 2019 Aug;24(8):1103-1110. doi: 10.1634/theoncologist.2018-0380. Epub 2019 Mar 19.
PubMed 30890623
Priantti JN, Vilbert M, de Moraes FCA, Madeira T, de Lima Santiago EM, Leighl NB, Cavalcante L, Karim NFA. Neurocognitive Adverse Events Related to Lorlatinib in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel). 2024 Jul 22;16(14):2611. doi: 10.3390/cancers16142611.
PubMed 39061249
Jiang J, Zhao C, Zhang F, Liu Z, Zhou K, Ren X, Wan Y. ALK inhibitors in ALK-rearranged non-small cell lung cancer with and without brain metastases: systematic review and network meta-analysis. BMJ Open. 2022 Sep 19;12(9):e060782. doi: 10.1136/bmjopen-2022-060782.
PubMed 36123063
Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. doi: 10.1016/S1470-2045(17)30680-0. Epub 2017 Oct 23.
PubMed 29074098