Analysis of the Effectiveness and Safety of Lorlatinib in Untreated ALK-Positive NSCLC Patients in a French Real-World Context
NCT Number: NCT06487078
Acronym: LOREA
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: ALK+ Non-Small-Cell Lung Carcinoma
Interventions: DRUG: Lorlatinib
Sponsor: Pfizer
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 90
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-07-15
Completion Date: 2028-11-30

Summary:
Analysis of the Effectiveness and Safety of Lorlatinib in Untreated ALK-Positive NSCLC Patients in a French Real-World context

Primary Outcome Measures: Progression-Free Survival (PFS), Time from inclusion to date of disease progression or death of any cause whichever occurs first., From time of Study Start up to 25 months
Secondary Outcome Measures: Overall Survival (OS), Time from inclusion to date of death from any cause., From time of Study Start up to 25 months|Objective Response Rate (ORR), proportion of patients with a Complete Response (CR) or Partial Response (PR) as a best response during the lorlatinib treatment. Responses to treatment will be defined according to investigator, From time of Study Start up to 24 months|Duration of Response (DR), time between the first documentation of objective response and the first documentation of disease progression or death from any cause whichever occurred first, for participants with a confirmed objective response of CR or PR., From time of Study Start up to 24 months|Intracranial Objective Response Rate (IC-ORR), proportion of patients with intracranial objective response of complete response (CR) or partial response (PR) as a best response in the subset of patients with at least 1 intracranial lesion assessed by investigator., From time of Study Start up to 24 months|Intracranial Time to Progression (IC-TTP), Time from inclusion to the date of the first documentation of disease progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases., From time of Study Start up to 24 months|Intracranial Duration of Response (IC-DR), time from the first documentation of intracranial OR to the first documentation of intracranial progressive disease (PD) or death due to any cause, whichever occurred first for participants with a confirmed objective response of CR or PR assessed by investigator., From time of Study Start up to 24 months|Duration of Treatment (DT), Time between inclusion and last dose of lorlatinib., From time of Study Start up to 25 months|Proportion of patients with extracranial progression and sites of progression, Based on Investigator's Assessment, From time of Study Start up to 24 months|Time to Treatment Failure (TTF), Time from date of treatment initiation to date of discontinuation of treatment for any reason, including progression of disease, treatment toxicity, and death from any cause whichever occurs first., From time of Study Start up to 24 months|Adverse Event (AE) as graded by NCI CTCAE v5), Frequency of patients experiencing treatment-emergent AEs (TEAEs), From time of Study Start up to 25 months|Number of Participants With Treatment-Emergent Adverse Events (AEs; Treatment-Related, Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. Treatment-related AEs were determined by investigators., From time of Study Start up to 25 months|Proportion of patients considered observant to treatment assessed by the compliance questionnaire., Self-administered questionnaire that provides a measure of compliance, At the start of cycle (each cyle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and then every 3 months - as long as 48 months|Proportion of patients experiencing a 10-points change from baseline in total score for the EORTC QLQ-C30, evaluate Health-related Quality of life (HRQoL) of ALK- positive locally advanced or metastatic NSCLC patients treated with lorlatinib in first-line using the EORTC QLQ-C30 questionnaires, At inclusion, At the start of Cycle (each cycle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months|Proportion of patients experiencing a 10-points change from baseline in total score for the EORT QLQ-LC13., Evaluate Health-related Quality of life (HRQoL) of ALK- positive locally advanced or metastatic NSCLC patients treated with lorlatinib in first-line using the EORTC QLQ -LC13 questionnaires, At inclusion, At the start of Cycle (each cycle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months|Patient Reported Outcome-informed CNS symptomatic toxicity:, frequency, severity and/or interference with daily activities, amount, presence/absence according to PRO-CTCAE questionnaires for mood (anxious/discouraged/sad), and attention/memory items (concentration/memory)., At inclusion, At the start of cycle (each cycle is 28 days) Cycle1Day15, Cycle2Day1, Cycle3Day1, Cycle4Day1 and every 3 months until the first year and then every 6 months - as long as 48 months|Proportion of patients experiencing grade III toxicities or progression and having an over- or under-exposure to lorlatinib., At each time point, a blood sample to provide plasma for determination of the plasma concentrations of lorlatinib., At baseline, at start of Cycle1Day15 (each cycle is 28 days), Month 3, Month 9 and every 6 months through the end of treatment, at time of first grade III of hyperlipidaemia and CNS toxicity onset, and at progression - as long as 48 months|Proportion of patients experiencing each kind of identified lorlatinib resistance mechanisms, Plasma samples collected at baseline and end of treatment, analyzed by next-generation sequencing, At baseline and at the date of first documented progression (as long as 48 months)