Longitudinal Assessment of Genomic Alterations and Clonal Evolution in ALK-positive NSCLC (Galileo Project) (GALILEO)

"GALILEO (Genomic ALteratIons and cLonal EvOlution in ALK+ NSCLC) - Valutazione Longitudinale Delle Alterazioni Genomiche e Clonali Nei Pazienti Affetti da Neoplasie Polmonari ALK-riarrangiate".

The scope of GALILEO project (Genomic ALteratIons and cLonal EvOlution in ALK+ NSCLC) is to explore the feasibility of genomic longitudinal evaluation for ALK+ NSCLC patients in Italian routine practice and provide a detailed overview of resistance mechanisms and clinical outcomes according to current standard treatments.

Study Overview

• Status: Recruiting
• Conditions: NSCLC Stage IV; ALK Gene Mutation; ALK Sensitizing Mutation
• Intervention / Treatment: Diagnostic test: Biopsy (tissue or liquid)

• Study Type: Observational
• Enrollment (Estimated): 108

Contacts and Locations

• Study Contact: Name: Emanuele Vita, MD; Phone Number: 3480510228; Email: dr.emanuele.vita@gmail.com
• Study Contact Backup: Name: EMILIO Bria, Prof.; Phone Number: 0630156318; Email: emilio.bria@policlinicogemelli.it

Study Locations

• Italy
  • Rome, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Gemelli IRCCS
    • Contact: Emilio Bria, Professor; Phone Number: +39 0630155202; Email: emilio.bria@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with newly diagnosed ALK+ NSCLC who are candidate to receive first-line therapy with II-III genaration ALK-inhibitor (alectinib, brigatinib or lorlatinib)

Description

Inclusion Criteria:

• a) histologically confirmed diagnosis of advanced NSCLC with ALK rearrangement detection by NGS (ALK+ NSCLCs patients detected at diagnosis by in hybridization (FISH), immunohistochememistry (IHC), or reverse transcriptase-PCR (RT-PCR) can be included if adequate tissue for NGS is available)

  b) to have received upfront treatment with alectinib, brigatinib or lorlatinib for at least 28 days

  c) ECOG PS 0-2

  d) adult patients (aged ≥ 18 years) at the moment of diagnosis

  e) signing of informed consent approved by the local Ethic Committee

Exclusion Criteria:

a) Diagnosis of lung cancer without ALK rearrangement

a) early withdrawn of treatment due to toxicity without evidence of radiological disease progression cannot be eligible for the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

ALK+ NSCLC; The GALILEO project is an Italian observational prospective cohort study on advanced ALK+ NSCLC patient progressing on first-line therapy with alectinib

Diagnostic test: Biopsy (tissue or liquid); At the time of diagnosis, all newly diagnosed ALK+ NSCLC patients eligible for first line treatment with alectinib or brigatinib or lorlatinib will be considered for the study. In case of progression, a multidisciplinary team (oncologists, interventional pneumologists and radiologists, surgeons) will discuss case-by-case the feasibility to procure an adequate biopsy from progressing lesions. Repeat biopsies will be performed within 2 weeks from multidisciplinary evaluation and before the start of subsequent treatment. If repeat biopsies are not technically or safely feasible or fail to yield sufficient material for genomic analysis, we will collect a whole blood drawn by venepuncture for the analysis of ctDNA.; Other Names: Lorlatinib; Alectinib; Brigatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with available NGS testing at diagnosis	Percentage of ALK+ patients with adeguate tissue for NGS after diagnosisc biopsy	5 years
Percentage of patients with available NGS re-testing after progession (either tissue or ctDNA) to first-line treatment with II-III generation ALK-Inhibitor	Percentage of patients who obtenied successfull NGS post-progression testing after re-biopsy or liquid biopsy	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS to first-line treatment with II-III generation ALK-inhibitor	Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years	5 years
PFS to first-line treatment with II-III generation ALK-inhibitor	Time from treatment start to death for any cause, assesed up to 5 years	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS to first-line treatment with II-III generation ALK-inhibitor	PFS to first-line, stratified according to ALK-rearrangement variants	Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
PFS to first-line treatment with II-III generation ALK-inhibitor	PFS to first-line, stratified according to NGS-based mutational profiling	Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
OS to first-line treatment with II-III generation ALK-inhibitor	OS to first-line, stratified according to ALK-rearrangement variants	Time from treatment start until the date of death from any cause, assessed up to 5 years
OS to first-line treatment with II-III generation ALK-inhibitor	OS to first-line, stratified according to NGS-based mutation profiling	Time from treatment start until the date of death from any cause, assessed up to 5 years
Incidence of secondary resistance mutations (SNVs) after first line treatment	Percentage of patients with SNV-based resistance diagnosed by tissue or liquid biopsy	5 years
PFS to lorlatinib according to secondary resistance mechanism	PFS to second-line lorlatinib, stratified according to type of resistance (SNV vs off-target)	Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: GIAMPAOLO TORTORA, Prof., Fondazione Policlinico Universitario A Gemelli

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: January 28, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; ALK mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Alectinib
• Other Study ID Numbers: 4906

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No