Clinical trial NCT02716311: Combination of Cetuximab With Afatinib for Patient With EGFR Mutated Lung Cancer
Official title: Phase II Study Evaluating the Combination of Cetuximab With Afatinib as First-line Treatment for Patients With EGFR Mutated Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: EGFR
Lung Cancer
Lead sponsor: Intergroupe Francophone de Cancerologie Thoracique
Sponsor class: OTHER
First posted: 2016-03-23
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Until recently, the first line treatment of metastatic Non Small Cell Lung Cancer (NSCLC) was a platine-based chemotherapy. It has been changed by the discovery of EGFR (Epidermal Growth Factor Receptor) mutations and associated treatment with Tyrosine Kinase Inhibitor (TKI) of EGFR. The superiority of EGFR TKI over chemotherapy for EGFR mutated patients has been proved in several phase III trials with gefitinib, erlotinib or afatinib.

Nevertheless, all patients will progress after 9 to 12 months of treatment due to the appearance of a treatment resistance.

Afatinib is an irreversible EGFR TKI. It binds to its receptor permanently.Contrary to erlotinib and gefitinb which inhibits only EGFR, afatinib inhibits the kinase activity of all HER family (Human Epidermal growth factor Receptor). Nevertheless, there is no proof that afatinib delay the appearance of resistance.

Cetuximab is a monoclonal antibody which binds specifically with EGFR. The double inhibition of EGFR by afatinib and cetuximab has demonstrated its efficacy in pre-clinical models. The hypothesis of this study is that the combination between cetuximab and afatinib will permit to delay or decrease the appearance of resistances.


Eligibility criteria: Principal Inclusion Criteria:

* Stage III or IV NSCLC, non irradiable non operable
* Non squamous NSCLC histologically or cytologically confirmed
* No previous treatment of NSCLC
* EGFR mutation (exon 19 deletion, L858R mutation, G719X , L861Q or S768I mutations or exon 19 insertion)
* Presence of at least one lesion that can be measured
* PS 0 or 1

Principal Exclusion Criteria:

* Symptomatic brain metastasis or requiring immediate radiotherapy
* T790M mutation or exon 20 insertion
* Radiotherapy less than 2 weeks prior randomization including symptomatic radiotherapy
* Interstitial pneumopathy

Primary outcomes:
measure: Time to Treatment Failure
timeFrame: 9 months
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 1 month
measure: Response Rate
timeFrame: 9 months
measure: Overall survival
timeFrame: 6 months
measure: Overall survival
timeFrame: 9 months
measure: Overall survival
timeFrame: 12 months
measure: Progression-Free Survival
timeFrame: 6 months
measure: Progression-Free Survival
timeFrame: 9 months
measure: Progression-Free Survival
timeFrame: 12 months
measure: Progression-Free Survival
timeFrame: 18 months
Other outcomes:
Locations:
city: Aix-en-Provence
country: France
facility: Centre Hospitalier du Pays d'Aix
city: Amiens
country: France
facility: Clinique de L'Europe
city: Angers
country: France
facility: Angers - CHU
city: Annecy
country: France
facility: Annecy - CH
city: Bordeaux
country: France
facility: Bordeaux - Institut Bergonié
city: Bordeaux
country: France
facility: Bordeaux - Polyclinique Nord
city: Boulogne-Billancourt
country: France
facility: Boulogne - Ambroise Paré
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand - CHU
city: Colmar
country: France
facility: CH
city: Grenoble
country: France
facility: CHRU Grenoble
city: Le Mans
country: France
facility: Centre Hospitalier - Pneumologie
city: Lille
country: France
facility: CHRU de Lille
city: Lille
country: France
facility: Lille - Polyclinique de la Louvière
city: Lyon
country: France
facility: Lyon - Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Montpellier
country: France
facility: Montpellier - GCS Centre de Cancérologie du Grand Montpellier
city: Mulhouse
country: France
facility: CH de Mulhouse
city: Nantes
country: France
facility: Nantes - ICO René Gauducheau
city: Nevers
country: France
facility: Nevers - CH
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orléans
country: France
facility: Orléans - Hôpital de la Source
city: Paris
country: France
facility: AP-HP Hopital Tenon - Pneumologie
city: Paris
country: France
facility: Paris - APHP Bichat
city: Paris
country: France
facility: Paris - APHP Saint-Louis
city: Pau
country: France
facility: Pau - CH
city: Pontoise
country: France
facility: Pontoise - CH
city: Saint-Quentin
country: France
facility: Centre Hospitalier
city: Strasbourg
country: France
facility: Nouvel Hopital Civil - Pneumologie
city: Toulon
country: France
facility: Centre Hospitalier Intercommunal
city: Toulon
country: France
facility: HIA Saint Anne
city: Tours
country: France
facility: Tours - CHU
city: Villefranche
country: France
facility: CH de Villefranche - Pneumologie
city: Villeneuve-d'Ascq
country: France
facility: Villeneuve d'Ascq - Hôpital Privé
Study officials:
affiliation: CHRU LILLE
name: Alexis CORTOT, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: AP-HP Hôpital Tenon, Paris
name: Jacques CADRANEL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cortot AB, Madroszyk A, Giroux-Leprieur E, Molinier O, Quoix E, Berard H, Otto J, Rault I, Moro-Sibilot D, Raimbourg J, Amour E, Morin F, Hureaux J, Moreau L, Debieuvre D, Morel H, Renault A, Pichon E, Huret B, Charpentier S, Denis MG, Cadranel J. First-Line Afatinib plus Cetuximab for EGFR-Mutant Non-Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study. Clin Cancer Res. 2021 Aug 1;27(15):4168-4176. doi: 10.1158/1078-0432.CCR-20-4604. Epub 2021 May 24.