Analysis of Biological Characteristics of Advanced ALK-rearranged NSCLC

Non-small Cell Lung Cancer Clinical Trial

— BIOEXALK  

Official title:

Biological Characterization of Advanced ALK-rearranged Non-small Cell Lung (NSCLC) Cancer Included in EXPLOREALK Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05122806
• Other study ID #: GroupeFDPC
• Secondary ID: GFPC 08-2020
• Status: Recruiting
• Phase: N/A
• Start date: September 22, 2021
• Est. completion date: June 30, 2027

Study information

• Verified date: October 2023
• Source: Groupe Francais De Pneumo-Cancerologie
• Contact: Florian GUISIER
• Phone: +33 2 32888079
• Email: florian.guisier[@]chu-rouen.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ALK Gene Rearrangement Positive
• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Genetic:
• RNAseq
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

Locations

Country	Name	City	State
France	Centre Hospitalier d'Aix en Provence	Aix En Provence
France	Pneumologie CHU	Amiens
France	Centre Hospitalier Universitaire	Angers
France	Centre Hospitalier d'Annecy	Annecy
France	Centre Hospitalier du Morvan	Brest
France	Centre François Baclesse	Caen
France	Pneumologie CH Métropole Savoie	Chambéry
France	Oncologie CLCC Jean Perrin	Clermont-Ferrand
France	Centre Hospitalier Intercommunal de Créteil	Creteil
France	Pneumologie CH Eure-Seine	Évreux
France	Pneumologie CHD Vendée	La Roche-sur-Yon
France	Pneumologie Hôpital Mignot	Le Chesnay
France	Pneumologie CH	Le Mans
France	Oncologie Centre Oscar Lombret	Lille
France	Pneumologie Hôpital Calmette	Lille
France	Pneumologie CHU Limoges	Limoges
France	Hôpital du Scorff	Lorient
France	Centre Léon Bérard	Lyon
France	Pneumologie Hôpital privé Jean Mermoz	Lyon
France	Oncologie Hôpital François Quesnay	Mantes-la-Jolie
France	Hôpital Nord	Marseille
France	Oncologie Institut Paoli Calmette	Marseille
France	Pneumologie Hôpital Européen	Marseille
France	Hôpital de Meaux	Meaux
France	Oncologie Institut du Cancer de Montpellier	Montpellier
France	Oncologie CH Morlaix	Morlaix
France	Pneumologie CHR	Orléans
France	Oncologie Institut Curie	Paris
France	Pneumologie Centre Hospitalier	Pau
France	Hôpital du Haut Leveque	Pessac
France	CHU Pontchailloux	Rennes
France	Hôpital Charles Nicolle	Rouen
France	Pneumologie Hôpital Yves Le Foll	Saint-Brieuc
France	Pneumologie CHU Félix Guyon	Saint-Denis	La Réunion
France	Institut Lucien Neuwirth	Saint-Priest-en-Jarez
France	Centre Paul Strauss	Strasbourg
France	Pneumologie Hôpital Foch	Suresnes
France	Pneumologie HIA	Talence
France	Hôpital d'Instruction des Armées Ste Anne	Toulon
France	Pneumologie Hôpital Sainte Musse	Toulon
France	Hôpital Larrey	Toulouse
France	Oncologie CH Bretagne-Atlantique	Vannes
France	Centre Hospitalier de Villefranche sur Saone	Villefranche Sur Saone
France	Oncologie Institut Gustave Roussy	Villejuif
France	Pneumologie CHI	Villeneuve-Saint-Georges

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Francais De Pneumo-Cancerologie	Takeda

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS assessed by local review using RECIST v1.1, defined as time from treatment initiation to the first clinical or radiological progression or death from any cause	From date of treatment initiation up to 72 months
Secondary	Overall Survival (OS)	OS defined as time from treatment initiation to death from any cause.	From date of treatment initiation up to 72 months
Secondary	Duration of Response (DoR)	DoR assessed by local review using RECIST v1.1, defined as time from treatment initiation to the first clinical or radiological progression, death, consent withdrawn, adverse event, protocol deviations, lost to follow-up, or initiation of a new line of anticancer therapy.	From date of treatment initiation up to 72 months
Secondary	Overall Response Rate (ORR)	ORR defined as objective response rate of complete response or partial response measured by local review RECIST v1.1.	From date of treatment initiation up to 72 months
Secondary	Circulating tumoral DNA (ctDNA) clearance on Progression Free Survival (PFS) of stage IV ALK-rearranged NSCLC patients	ctDNA clearance will be determine as clearance of the fusion when detectable and/or clearance of relevant mutations when fusion not detected	From date of treatment initiation up to 72 months
Secondary	Circulating tumoral DNA (ctDNA) clearance on Overall Survival (OS) of stage IV ALK-rearranged NSCLC patients	ctDNA clearance will be determine as clearance of the fusion when detectable and/or clearance of relevant mutations when fusion not detected	From date of treatment initiation up to 72 months
Secondary	Circulating tumoral DNA (ctDNA) clearance on Duration of Response (DoR) of stage IV ALK-rearranged NSCLC patients	ctDNA clearance will be determine as clearance of the fusion when detectable and/or clearance of relevant mutations when fusion not detected	From date of treatment initiation up to 72 months
Secondary	Circulating tumoral DNA (ctDNA) clearance on Overall Response Rate (ORR) of stage IV ALK-rearranged NSCLC patients	ctDNA clearance will be determine as clearance of the fusion when detectable and/or clearance of relevant mutations when fusion not detected	From date of treatment initiation up to 72 months
Secondary	Description of mechanisms of resistance associated with first-line tyrosine kinase inhibitors	The following mechanisms of resistance will be assessed: secondary mutations on ALK, mutations or translocations on other genes of interest, histological transformations	From date of treatment initiation up to 72 months
Secondary	Description of mechanism of resistance associated with each ALK-fusion partner	The following mechanisms of resistance will be assessed: secondary mutations on ALK, mutations or translocations on other genes of interest, histological transformations	From date of treatment initiation up to 72 months
Secondary	Concordance between ALK fusion partner and co-mutations	ALK fusion partner and co-mutation identifications based on liquid and tissue biopsies at Baseline	From date of treatment initiation up to 72 months
Secondary	Impact of presence or absence of serum Anti-ALK antibodies at diagnosis on OS		From date of treatment initiation up to 72 months