Clinical trial NCT06487078: Analysis of the Effectiveness and Safety of Lorlatinib in Untreated ALK-Positive NSCLC Patients in a French Real-World Context
Official title: LOREA: ANALYSIS OF THE EFFECTIVENESS AND SAFETY OF LORLATINIB IN UNTREATED ALK-POSITIVE NSCLC PATIENTS IN A FRENCH REAL-WORLD CONTEXT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ALK+ Non-Small-Cell Lung Carcinoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-07-05
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria: Participants are eligible to be included in the study only if all the following criteria apply:

* Patients (male or female) 18 years of age or older at age inclusion
* Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic (TNM 8th classification) ALK-positive NSCLC (IHC 3+/FISH positive/transcriptomic method)
* Complete radiological evaluation has to be performed before the start of lorlatinib by contrast enhanced CT-scan of thorax and upper abdomen and brain MRI, as per routine care
* Patients with ECOG performance status grade 0, 1, or 2

Exclusion Criteria: Participants are excluded from the study if any of the following criteria Apply

* Evidence of active malignancy within the last 2 years prior to inclusion (other than NSCLC, non-melanoma skin cancer, cervical in situ cancer, papillary thyroid cancer, lobular carcinoma in situ/ductal carcinoma in situ (LCIS/DCIS) of the breast, or localized prostate cancer).
* Patients who have previously received adjuvant ALK TKI therapy (unless metastatic relapse occurs more than one year after completion of adjuvant therapy).
* Patients who have previously received systemic NSCLC therapy in metastatic condition.
* Patients using any of the following food or drugs within 12 days prior to the first dose of lorlatinib:

  * known strong CYP3A inhibitors
  * known strong CYP3A inducers
  * known P gp substrates with a narrow therapeutic index
* Patients with any medical or psychiatric condition, or that may, in the investigator's judgment, increase the risk of study participation or make the participant inappropriate for the study.
* Positive pregnancy test for females of childbearing potential.
* Breastfeeding and childbearing potential female unwilling/unable to use a highly effective contraception method for the study duration and for at least 35 days after the last dose of lorlatinib
* Fertile male patients unwilling/unable to use a highly effective method of contraception for the duration of the study and for at least 97 days after the last dose of lorlatinib.
* Patients participating in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
* Patients deprived of their liberty, under protective custody or guardianship or unable to provide signed consent.
* Patients not affiliated to the French social security system.
* Patients opposed to the collection of their data.
* Patients willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow-up.
* Patients judged inapt to respond to the questions required for the study due to linguistical, psychological, social, or geographical reasons.
* Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From time of Study Start up to 25 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From time of Study Start up to 25 months
measure: Objective Response Rate (ORR)
timeFrame: From time of Study Start up to 24 months
measure: Duration of Response (DR)
timeFrame: From time of Study Start up to 24 months
measure: Intracranial Objective Response Rate (IC-ORR)
timeFrame: From time of Study Start up to 24 months
measure: Intracranial Time to Progression (IC-TTP)
timeFrame: From time of Study Start up to 24 months
measure: Intracranial Duration of Response (IC-DR)
timeFrame: From time of Study Start up to 24 months
measure: Duration of Treatment (DT)
timeFrame: From time of Study Start up to 25 months
measure: Proportion of patients with extracranial progression and sites of progression
timeFrame: From time of Study Start up to 24 months
measure: Time to Treatment Failure (TTF)
timeFrame: From time of Study Start up to 24 months
measure: Adverse Event (AE) as graded by NCI CTCAE v5)
timeFrame: From time of Study Start up to 25 months
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs; Treatment-Related
timeFrame: From time of Study Start up to 25 months
measure: Proportion of patients considered observant to treatment assessed by the compliance questionnaire.
timeFrame: At the start of cycle (each cyle is 28 days) Cycle2Day1, Cycle3Day1, Cycle4Day1 and then every 3 months - as long as 48 months
measure: Proportion of patients experiencing a 10-points change from baseline in total score for the EORTC QLQ-C30
timeFrame: 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
measure: Proportion of patients experiencing a 10-points change from baseline in total score for the EORT QLQ-LC13.
timeFrame: 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
measure: Patient Reported Outcome-informed CNS symptomatic toxicity:
timeFrame: 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
measure: Proportion of patients experiencing grade III toxicities or progression and having an over- or under-exposure to lorlatinib.
timeFrame: 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
measure: Proportion of patients experiencing each kind of identified lorlatinib resistance mechanisms
timeFrame: At baseline and at the date of first documented progression (as long as 48 months)
Other outcomes:
Locations:
city: Reims Cedex
country: France
facility: Institut Godinot
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: