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

Pfizer90 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

ALK+ Non-Small-Cell Lung Carcinoma

Interventions

LorlatinibDRUG

ALK-positive NSCL treatment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (31)

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Time from inclusion to date of disease progression or death of any cause whichever occurs first.

Time frame: From time of Study Start up to 25 months

Secondary Outcomes

Overall Survival (OS)

Time from inclusion to date of death from any cause.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From time of Study Start up to 24 months

Central Contacts

Pfizer CT.gov Call Center

CONTACT

1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Institut Curie

Paris, Paris, France

RECRUITING

Centre Hospitalier du Pays d AIX

Aix-en-Provence, France

RECRUITING

CH ALBI

Albi, France

RECRUITING

Chu Amiens Sud

Amiens, France

RECRUITING

Ch Avignon

Avignon, France

NOT_YET_RECRUITING

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, France

NOT_YET_RECRUITING

Institut Bergonie

Bordeaux, France

NOT_YET_RECRUITING

Hopital Morvan

Brest, France

NOT_YET_RECRUITING

CHIC

Créteil, France

RECRUITING

Clcc Georges Francois Leclerc

Dijon, France

RECRUITING

...and 21 more locations

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.

Time frame: From time of Study Start up to 24 months

Duration of Treatment (DT)

Time between inclusion and last dose of lorlatinib.

Time frame: From time of Study Start up to 25 months

Proportion of patients with extracranial progression and sites of progression

Based on Investigator's Assessment

Time frame: 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.

Time frame: 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)

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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).

Time frame: 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.

Time frame: 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

Time frame: At baseline and at the date of first documented progression (as long as 48 months)