Vortioxetine for Cognitive Function in ALK-positive NSCLC Treated With Lorlatinib
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Advanced ALK/ROS1-positive NSCLC, Carcinoma, Non-Small-Cell Lung (NSCLC), Lung Adenocarcinoma, ALK-positive Non-small Cell Lung Cancer (NSCLC). Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Colombia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Potential Effect of Vortioxetine on Cognitive Functioning of Patients With ALK-positive Non-Small Cell Lung Cancer Treated With Lorlatinib
Overview
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 outcome measures
- Psychomotor Speed [Time frame: Baseline, Week 6, Week 12]
- Processing Speed and Visual Attention [Time frame: Baseline, Week 6, Week 12]
- Executive Function and Cognitive Flexibility [Time frame: Baseline, Week 6, Week 12]
- Selective and Sustained Attention [Time frame: Baseline, Week 6, Week 12]
- Working Memory [Time frame: Baseline, Week 6, Week 12]
- Processing Speed [Time frame: Baseline, Week 6, Week 12]
- Verbal Learning and Memory [Time frame: Baseline, Week 6, Week 12]
- Language [Time frame: Baseline, Week 6, Week 12]
- Language [Time frame: Baseline, Week 6, Week 12]
- Frontal Lobe and Executive Function [Time frame: Baseline, Week 6, Week 12]
Secondary outcome measures (12)
- Depressive Symptoms [Time frame: Baseline, Week 6, Week 12, Month 6]
- Depressive Symptoms [Time frame: Baseline, Week 6, Week 12]
- Health-Related Quality of Life [Time frame: Baseline, Month 1, 2, 3, 6, 12]
- Health-Related Quality of Life [Time frame: Baseline, Month 1, 2, 3, 6, 12]
- Life Satisfaction [Time frame: Baseline, Month 1, 2, 3, 6, 12]
- Health Utility [Time frame: 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]
- Functional Capacity [Time frame: Baseline, Week 6, Week 12]
- Work Limitations [Time frame: Baseline, Week 6, Week 12, Month 6]
- Cognitive and Physical Functioning [Time frame: Baseline, Week 6, Week 12]
- Tumor Response to Lorlatinib [Time frame: Month 2, Month 6, Month 12]
- Adverse Events [Time frame: All scheduled visits, from baseline through 30 days post-last visit]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Case-only
Study locations
Colombia · 1 center
- Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo CTIC — Bogotá
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/s00213-019-052 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
- 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. PMID 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 PMID 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. PMID 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. PMID 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. PMID 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. PMID 26752591
Identifiers
NCT: NCT07633626 · Vortioxetina