Vortioxetine for Cognitive Function in ALK-positive NSCLC Treated With Lorlatinib
4 de junio de 2026 actualizado por: 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.
Descripción general del estudio
Estado
Reclutamiento
Tipo de estudio
De observación
Inscripción (Estimado)
24
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Felipe Canro, MD
- Número de teléfono: +57 310 8593083
- Correo electrónico: felipe.canro@gmail.com
Ubicaciones de estudio
-
-
-
Bogotá, Colombia, 110131
- Reclutamiento
- Centro de Tratamiento e Investigación sobre Cancer Luis Carlos Sarmiento Angulo Ctic
-
Contacto:
- Liliana Gutiérrez, RN, MSc
- Número de teléfono: +573003768158
- Correo electrónico: lgutierrez@fctic.org
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Método de muestreo
Muestra no probabilística
Población de estudio
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.
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Psychomotor Speed
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Depressive Symptoms
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
- 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.
- Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Perol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. doi: 10.1056/NEJMoa1704795. Epub 2017 Jun 6.
- Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. doi: 10.1056/NEJMoa2027187.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Petrelli F, Lazzari C, Ardito R, Borgonovo K, Bulotta A, Conti B, Cabiddu M, Capitanio JF, Brighenti M, Ghilardi M, Gianni L, Barni S, Gregorc V. Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies. PLoS One. 2018 Jul 27;13(7):e0201425. doi: 10.1371/journal.pone.0201425. eCollection 2018.
- Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, Uhlmann EJ, Wong ET, Dahlberg SE, Huberman MS, Costa DB. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer. 2015 Apr;88(1):108-11. doi: 10.1016/j.lungcan.2015.01.020. Epub 2015 Feb 4.
- 18. Japanese Ministry of Health, Labor and Welfare . Report on the Deliberation Results. www.pmda.go.jp/files/000228981.pdf
- 17. European Medicines Agency. Lorviqua. www.ema.europa.eu/en/medicines/human/EPAR/lorviqua
- 16. US FDA . FDA approves Lorlatinib for metastatic ALK-positive NSCLC. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-Lorlatinib-metastatic-alk-positive-nsclc
- Syed YY. Lorlatinib: First Global Approval. Drugs. 2019 Jan;79(1):93-98. doi: 10.1007/s40265-018-1041-0.
- Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, Chiari R, Bearz A, Lin CC, Gadgeel SM, Riely GJ, Tan EH, Seto T, James LP, Clancy JS, Abbattista A, Martini JF, Chen J, Peltz G, Thurm H, Ou SI, Shaw AT. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018 Dec;19(12):1654-1667. doi: 10.1016/S1470-2045(18)30649-1. Epub 2018 Nov 6.
- Pacheco JM, Gao D, Smith D, Purcell T, Hancock M, Bunn P, Robin T, Liu A, Karam S, Gaspar L, Kavanagh B, Rusthoven C, Aisner D, Doebele R, Camidge DR. Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non-Small Cell Lung Cancer. J Thorac Oncol. 2019 Apr;14(4):691-700. doi: 10.1016/j.jtho.2018.12.014. Epub 2018 Dec 30.
- Sellmann L, Fenchel K, Dempke WC. Improved overall survival following tyrosine kinase inhibitor treatment in advanced or metastatic non-small-cell lung cancer-the Holy Grail in cancer treatment? Transl Lung Cancer Res. 2015 Jun;4(3):223-7. doi: 10.3978/j.issn.2218-6751.2015.03.01.
- Morgensztern D, Ng SH, Gao F, Govindan R. Trends in stage distribution for patients with non-small cell lung cancer: a National Cancer Database survey. J Thorac Oncol. 2010 Jan;5(1):29-33. doi: 10.1097/JTO.0b013e3181c5920c.
- 10. American Cancer Society . Lung cancer survival rates. www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html
- Barrios CH, Werutsky G, Martinez-Mesa J. The global conduct of cancer clinical trials: challenges and opportunities. Am Soc Clin Oncol Educ Book. 2015:e132-9. doi: 10.14694/EdBook_AM.2015.35.e132.
- Parra-Medina R, Castaneda-Gonzalez JP, Montoya L, Paula Gomez-Gomez M, Clavijo Cabezas D, Plazas Vargas M. Prevalence of oncogenic driver mutations in Hispanics/Latin patients with lung cancer. A systematic review and meta-analysis. Lung Cancer. 2023 Nov;185:107378. doi: 10.1016/j.lungcan.2023.107378. Epub 2023 Sep 15.
- Arrieta O, Cardona AF, Bramuglia G, Cruz-Rico G, Corrales L, Martin C, Imaz-Olguin V, Castillo O, Cuello M, Rojas-Bilbao E, Casas G, Fernandez C, Aren Frontera O, Denninghoff V, Recondo G, Aviles-Salas A, Mas-Lopez LA, Oblitas G, Rojas L, Piottante A, Jimenez-Garcia E, Sanchez-Sosa S, Saenz-Frias J, Lupera H, Ramirez-Tirado LA, Vargas C, Carranza H, Astudillo H, Wills LB, Pichelbaur E, Raez LE; on behalf of the CLICaP. Molecular Epidemiology of ALK Rearrangements in Advanced Lung Adenocarcinoma in Latin America. Oncology. 2019;96(4):207-216. doi: 10.1159/000493733. Epub 2018 Nov 26.
- Mazieres J, Iadeluca L, Shaw AT, Solomon BJ, Bauer TM, de Marinis F, Felip E, Goto Y, Kim DW, Mok T, Reisman A, Thurm H, Polli AM, Liu G. Patient-reported outcomes from the randomized phase 3 CROWN study of first-line lorlatinib versus crizotinib in advanced ALK-positive non-small cell lung cancer. Lung Cancer. 2022 Dec;174:146-156. doi: 10.1016/j.lungcan.2022.11.004. Epub 2022 Nov 7.
- Solomon BJ, Liu G, Felip E, Mok TSK, Soo RA, Mazieres J, Shaw AT, de Marinis F, Goto Y, Wu YL, Kim DW, Martini JF, Messina R, Paolini J, Polli A, Thomaidou D, Toffalorio F, Bauer TM. Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol. 2024 Oct 10;42(29):3400-3409. doi: 10.1200/JCO.24.00581. Epub 2024 May 31.
- Solomon BJ, Bauer TM, Mok TSK, Liu G, Mazieres J, de Marinis F, Goto Y, Kim DW, Wu YL, Jassem J, Lopez FL, Soo RA, Shaw AT, Polli A, Messina R, Iadeluca L, Toffalorio F, Felip E. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023 Apr;11(4):354-366. doi: 10.1016/S2213-2600(22)00437-4. Epub 2022 Dec 16.
- Zia V, Lengyel CG, Tajima CC, de Mello RA. Advancements of ALK inhibition of non-small cell lung cancer: a literature review. Transl Lung Cancer Res. 2023 Jul 31;12(7):1563-1574. doi: 10.21037/tlcr-22-619. Epub 2023 Jul 4.
- Barta JA, Powell CA, Wisnivesky JP. Global Epidemiology of Lung Cancer. Ann Glob Health. 2019 Jan 22;85(1):8. doi: 10.5334/aogh.2419.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
10 de marzo de 2026
Finalización primaria (Estimado)
10 de marzo de 2027
Finalización del estudio (Estimado)
10 de noviembre de 2027
Fechas de registro del estudio
Enviado por primera vez
14 de abril de 2026
Primero enviado que cumplió con los criterios de control de calidad
4 de junio de 2026
Publicado por primera vez (Actual)
8 de junio de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
8 de junio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
4 de junio de 2026
Última verificación
1 de junio de 2026
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Desordenes mentales
- Neoplasias por sitio
- Neoplasias
- Síntomas de comportamiento
- Enfermedades de las vías respiratorias
- Neoplasias por tipo histológico
- Trastornos neurocognitivos
- Enfermedades pulmonares
- Trastornos cognitivos
- Neoplasias Glandulares y Epiteliales
- Adenocarcinoma
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Neoplasias Pulmonares
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Comportamiento
- Adenocarcinoma de pulmón
- Disfunción congnitiva
- Carcinoma
- Depresión
- Carcinoma de pulmón de células no pequeñas
Otros números de identificación del estudio
- Vortioxetina
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
INDECISO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .