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

NSCLC Stage IV Clinical Trial

— GALILEO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06234579
• Other study ID #: 4906
• Status: Recruiting
• Start date: July 12, 2021
• Est. completion date: July 31, 2026

Study information

• Verified date: January 2024
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: Emanuele Vita, MD
• Phone: 3480510228
• Email: dr.emanuele.vita[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: July 31, 2026
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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a) early withdrawn of treatment due to toxicity without evidence of radiological disease progression cannot be eligible for the study

Related Conditions & MeSH terms

• ALK Gene Mutation
• Carcinoma, Non-Small-Cell Lung
• NSCLC Stage IV

Intervention

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.

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Gemelli IRCCS	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	Percentage of patients with available NGS testing at diagnosis	Percentage of ALK+ patients with adeguate tissue for NGS after diagnosisc biopsy	5 years
Primary	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	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
Secondary	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