NCT02716311

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
118

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started May 2016

Longer than P75 for phase_2

Geographic Reach
1 country

33 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 30, 2015

Completed
4 months until next milestone

First Posted

Study publicly available on registry

March 23, 2016

Completed
1 month until next milestone

Study Start

First participant enrolled

May 1, 2016

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2019

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 7, 2021

Completed
Last Updated

August 11, 2022

Status Verified

August 1, 2022

Enrollment Period

2.8 years

First QC Date

November 30, 2015

Last Update Submit

August 9, 2022

Conditions

Keywords

EGFRLung Cancer

Outcome Measures

Primary Outcomes (1)

  • Time to Treatment Failure

    9 months

Secondary Outcomes (9)

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    1 month

  • Response Rate

    9 months

  • Overall survival

    6 months

  • Overall survival

    9 months

  • Overall survival

    12 months

  • +4 more secondary outcomes

Study Arms (2)

Afatinib

OTHER

Afatinib 40 mg/d until progression

Drug: Afatinib

Afatinib + cetuximab

EXPERIMENTAL

Afatinib 40 mg/d until progression + cetuximab 500 mg/m² every 2 weeks during 6 months (beginning at D15 at 250 mg/m²)

Drug: AfatinibDrug: Cetuximab

Interventions

AfatinibAfatinib + cetuximab
Afatinib + cetuximab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (33)

Centre Hospitalier du Pays d'Aix

Aix-en-Provence, France

Location

Clinique de L'Europe

Amiens, France

Location

Angers - CHU

Angers, France

Location

Annecy - CH

Annecy, 74374, France

Location

Bordeaux - Institut Bergonié

Bordeaux, France

Location

Bordeaux - Polyclinique Nord

Bordeaux, France

Location

Boulogne - Ambroise Paré

Boulogne-Billancourt, France

Location

Clermont-Ferrand - CHU

Clermont-Ferrand, France

Location

CH

Colmar, France

Location

CHRU Grenoble

Grenoble, France

Location

Centre Hospitalier - Pneumologie

Le Mans, 72000, France

Location

CHRU de Lille

Lille, France

Location

Lille - Polyclinique de la Louvière

Lille, France

Location

Lyon - Hôpital Privé Jean Mermoz

Lyon, France

Location

Institut Paoli Calmette

Marseille, France

Location

Montpellier - GCS Centre de Cancérologie du Grand Montpellier

Montpellier, France

Location

CH de Mulhouse

Mulhouse, France

Location

Nantes - ICO René Gauducheau

Nantes, France

Location

Nevers - CH

Nevers, 58033, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Orléans - Hôpital de la Source

Orléans, France

Location

AP-HP Hopital Tenon - Pneumologie

Paris, 75020, France

Location

Paris - APHP Bichat

Paris, France

Location

Paris - APHP Saint-Louis

Paris, France

Location

Pau - CH

Pau, 64046, France

Location

Pontoise - CH

Pontoise, France

Location

Centre Hospitalier

Saint-Quentin, France

Location

Nouvel Hopital Civil - Pneumologie

Strasbourg, 63000, France

Location

Centre Hospitalier Intercommunal

Toulon, France

Location

HIA Saint Anne

Toulon, France

Location

Tours - CHU

Tours, 37000, France

Location

CH de Villefranche - Pneumologie

Villefranche, France

Location

Villeneuve d'Ascq - Hôpital Privé

Villeneuve-d'Ascq, France

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungLung Neoplasms

Interventions

AfatinibCetuximab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

AmidesOrganic ChemicalsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Alexis CORTOT, MD, PhD

    CHRU LILLE

    PRINCIPAL INVESTIGATOR
  • Jacques CADRANEL, MD, PhD

    AP-HP Hôpital Tenon, Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 30, 2015

First Posted

March 23, 2016

Study Start

May 1, 2016

Primary Completion

February 1, 2019

Study Completion

April 7, 2021

Last Updated

August 11, 2022

Record last verified: 2022-08

Locations