Clinical trial NCT05122806: Analysis of Biological Characteristics of Advanced ALK-rearranged NSCLC
Official title: Biological Characterization of Advanced ALK-rearranged Non-small Cell Lung (NSCLC) Cancer Included in EXPLOREALK Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non-small Cell Lung Cancer
ALK Gene Rearrangement Positive
Lead sponsor: Groupe Francais De Pneumo-Cancerologie
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2021-11-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: BioEXALK is a prospective study evaluating the biological characteristics of advanced ALK-rearranged NSCLC treated with next generation TKIs in first line, included in the national EXPLORE ALK cohort (GFPC 03-2019), a non-interventional, national, multi-center cohort of ALK-rearranged NSCLC patients.

BioExALK study will be proposed to every patient included in the Explore ALK GFPC 03-2019 study.

Biological analysis will be performed on tumor tissue at diagnosis and at the time of disease progression when available and on circulating tumor DNA (ctDNA).

For plasma testing, after obtained patient consent, blood samples will be taken and analyzed at the Léon Bérard Center (Lyon).

Biological analysis on tissue obtained at diagnosis and at disease progression will be collected and be sent for centralized analysis to the Rouen University Hospital.

Detailed description: BioEXALK is a prospective study evaluating the biological characteristics of advanced ALK-rearranged NSCLC treated with new generation TKIs in first line, included in the national EXPLORE ALK cohort (GFPC 03-2019).

Explore ALK GFPC 03-2019 is a non-interventional, national, multi-center cohort of ALK-rearranged NSCLC patients, whose RCB reference is 2020-A00771-38 and which obtained an approval from the IDF II Ethic Committee on 25/05/2020. Biological analysis will be performed on tissue at diagnosis and at the time of disease progression when available and on circulating tumor DNA (ctDNA) on three timepoints (diagnosis, at first tumor evaluation and at the time of disease progression).

* Tissue : RNAseq will be performed on tumor biopsy (10 slides of 5 microns) to identify the ALK fusion partner and its variant and associated co-mutations..
* ctDNA : NGS panel on DNA including a large panel of fusions and mutations will be performed on blood samples (30mL on EDTA or STRECKs tubes) at diagnosis, at the time of the first evaluation and at the time of progression).

For plasma testing, after obtained patient consent, blood samples (35mL on EDTA or STRECKs tubes) at diagnosis, at the first evaluation and at disease progression will be taken.

The ALKis include alectinib and brigatinib as first-line therapy or other drugs with marketing authorizations (lorlatinib, entrectinib) or in early access programs (EAPs).

Liquid biopsies will be analyzed with a NGS panel allowing the identification of ALK fusion partners and resistance mechanisms (mutations, fusions, copy number variations). Samples will be sent for centralized analysis to the Léon Bérard Center (Lyon).

For biological analysis on tissue obtained at diagnosis, the ALK fusion partner and its variant will be identified by RNAseq. Whenever a tissue re-biopsy is performed at the time of disease progression as part of the standard of care management of the patient, the remaining tissue sample will be collected as part of the BioExALK study, so that RNAseq analysis will be performed to look for resistance mechanisms. Tissue samples (10 slides of 5 microns) will be sent for centralized analysis to the Rouen University Hospital.

Eligibility criteria: Inclusion Criteria:

* Stage IIIB/IV NSCLC non eligible to locoregional treatment with curative intent
* ALK rearrangement confirmed by IHC and/or FISH or NGS according to local methods
* Patient included in the EXPLORE ALK study
* Age \> or = 18 years
* Patient treated with first-line new generation ALKi
* Patient agrees to sign an informed consent form and to collect blood samples at inclusion, first tumor evaluation and progression and for whom tumor biopsy at diagnosis is available
* Patient enrolled in the french National Health Insurance program or with a third- party payer

Exclusion Criteria:

* Patients who do not wish to participate in Bioexalk
* Patients under guardianship

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From date of treatment initiation up to 72 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of treatment initiation up to 72 months
measure: Duration of Response (DoR)
timeFrame: From date of treatment initiation up to 72 months
measure: Overall Response Rate (ORR)
timeFrame: From date of treatment initiation up to 72 months
measure: Circulating tumoral DNA (ctDNA) clearance on Progression Free Survival (PFS) of stage IV ALK-rearranged NSCLC patients
timeFrame: From date of treatment initiation up to 72 months
measure: Circulating tumoral DNA (ctDNA) clearance on Overall Survival (OS) of stage IV ALK-rearranged NSCLC patients
timeFrame: From date of treatment initiation up to 72 months
measure: Circulating tumoral DNA (ctDNA) clearance on Duration of Response (DoR) of stage IV ALK-rearranged NSCLC patients
timeFrame: From date of treatment initiation up to 72 months
measure: Circulating tumoral DNA (ctDNA) clearance on Overall Response Rate (ORR) of stage IV ALK-rearranged NSCLC patients
timeFrame: From date of treatment initiation up to 72 months
measure: Description of mechanisms of resistance associated with first-line tyrosine kinase inhibitors
timeFrame: From date of treatment initiation up to 72 months
measure: Description of mechanism of resistance associated with each ALK-fusion partner
timeFrame: From date of treatment initiation up to 72 months
measure: Concordance between ALK fusion partner and co-mutations
timeFrame: From date of treatment initiation up to 72 months
measure: Impact of presence or absence of serum Anti-ALK antibodies at diagnosis on OS
timeFrame: From date of treatment initiation up to 72 months
Other outcomes:
Locations:
city: Saint-Denis
country: France
facility: Pneumologie CHU Félix Guyon
state: La Réunion
city: Aix En Provence
country: France
facility: Centre Hospitalier d'Aix en Provence
city: Amiens
country: France
facility: Pneumologie CHU
city: Angers
country: France
facility: Centre Hospitalier Universitaire
city: Annecy
country: France
facility: Centre Hospitalier d'Annecy
city: Brest
country: France
facility: Centre Hospitalier du Morvan
city: Caen
country: France
facility: Centre François Baclesse
city: Chambéry
country: France
facility: Pneumologie CH Métropole Savoie
city: Clermont-Ferrand
country: France
facility: Oncologie CLCC Jean Perrin
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: La Roche-sur-Yon
country: France
facility: Pneumologie CHD Vendée
city: Le Chesnay
country: France
facility: Pneumologie Hôpital Mignot
city: Le Mans
country: France
facility: Pneumologie CH
city: Lille
country: France
facility: Oncologie Centre Oscar Lombret
city: Lille
country: France
facility: Pneumologie Hôpital Calmette
city: Limoges
country: France
facility: Pneumologie CHU Limoges
city: Lorient
country: France
facility: Hôpital du Scorff
city: Lyon
country: France
facility: Pneumologie Hôpital privé Jean Mermoz
city: Lyon
country: France
facility: Centre Léon Bérard
city: Mantes-la-Jolie
country: France
facility: Oncologie Hôpital François Quesnay
city: Marseille
country: France
facility: Pneumologie Hôpital Européen
city: Marseille
country: France
facility: Oncologie Institut Paoli Calmette
city: Marseille
country: France
facility: Hôpital Nord
city: Meaux
country: France
facility: Hôpital de Meaux
city: Montpellier
country: France
facility: Oncologie Institut du Cancer de Montpellier
city: Morlaix
country: France
facility: Oncologie CH Morlaix
city: Orléans
country: France
facility: Pneumologie CHR
city: Paris
country: France
facility: Oncologie Institut Curie
city: Pau
country: France
facility: Pneumologie Centre Hospitalier
city: Pessac
country: France
facility: Hôpital du Haut Leveque
city: Rennes
country: France
facility: CHU Pontchailloux
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Saint-Brieuc
country: France
facility: Pneumologie Hôpital Yves Le Foll
city: Saint-Priest-en-Jarez
country: France
facility: Institut Lucien Neuwirth
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Suresnes
country: France
facility: Pneumologie Hôpital Foch
city: Talence
country: France
facility: Pneumologie HIA
city: Toulon
country: France
facility: Pneumologie Hôpital Sainte Musse
city: Toulon
country: France
facility: Hôpital d'Instruction des Armées Ste Anne
city: Toulouse
country: France
facility: Hôpital Larrey
city: Vannes
country: France
facility: Oncologie CH Bretagne-Atlantique
city: Villefranche Sur Saone
country: France
facility: Centre Hospitalier de Villefranche sur Saone
city: Villejuif
country: France
facility: Oncologie Institut Gustave Roussy
city: Villeneuve-Saint-Georges
country: France
facility: Pneumologie CHI
city: Évreux
country: France
facility: Pneumologie CH Eure-Seine
Study officials:
affiliation: Groupe Francais De Pneumo-Cancerologie
name: Christos CHOUAID
role: STUDY_DIRECTOR
References: