Combination of Cetuximab With Afatinib for Patient With EGFR Mutated Lung Cancer (ACE-Lung)

August 9, 2022 updated by: Intergroupe Francophone de Cancerologie Thoracique

Phase II Study Evaluating the Combination of Cetuximab With Afatinib as First-line Treatment for Patients With EGFR Mutated Non Small Cell Lung Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

118

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Aix-en-Provence, France
        • Centre Hospitalier du Pays d'Aix
      • Amiens, France
        • Clinique de l'Europe
      • Angers, France
        • Angers - CHU
      • Annecy, France, 74374
        • Annecy - CH
      • Bordeaux, France
        • Bordeaux - Polyclinique Nord
      • Bordeaux, France
        • Bordeaux - Institut Bergonié
      • Boulogne-Billancourt, France
        • Boulogne - Ambroise Paré
      • Clermont-Ferrand, France
        • Clermont-Ferrand - CHU
      • Colmar, France
        • CH
      • Grenoble, France
        • CHRU Grenoble
      • Le Mans, France, 72000
        • Centre Hospitalier - Pneumologie
      • Lille, France
        • CHRU de Lille
      • Lille, France
        • Lille - Polyclinique de la Louvière
      • Lyon, France
        • Lyon - Hôpital Privé Jean Mermoz
      • Marseille, France
        • Institut Paoli Calmette
      • Montpellier, France
        • Montpellier - GCS Centre de Cancérologie du Grand Montpellier
      • Mulhouse, France
        • CH de Mulhouse
      • Nantes, France
        • Nantes - ICO René Gauducheau
      • Nevers, France, 58033
        • Nevers - CH
      • Nice, France
        • Centre Antoine Lacassagne
      • Orléans, France
        • Orléans - Hôpital de la Source
      • Paris, France
        • Paris - APHP Bichat
      • Paris, France, 75020
        • AP-HP Hopital Tenon - Pneumologie
      • Paris, France
        • Paris - APHP Saint-Louis
      • Pau, France, 64046
        • Pau - CH
      • Pontoise, France
        • Pontoise - CH
      • Saint-Quentin, France
        • Centre Hospitalier
      • Strasbourg, France, 63000
        • Nouvel Hopital Civil - Pneumologie
      • Toulon, France
        • Centre Hospitalier Intercommunal
      • Toulon, France
        • HIA Saint Anne
      • Tours, France, 37000
        • Tours - CHU
      • Villefranche, France
        • CH de Villefranche - Pneumologie
      • Villeneuve-d'Ascq, France
        • Villeneuve d'Ascq - Hôpital Privé

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Afatinib
Afatinib 40 mg/d until progression
Drug: Afatinib
EXPERIMENTAL: Afatinib + cetuximab
Afatinib 40 mg/d until progression + cetuximab 500 mg/m² every 2 weeks during 6 months (beginning at D15 at 250 mg/m²)
Drug: Cetuximab
Drug: Afatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to Treatment Failure
Time Frame: 9 months
9 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 12 months
12 months
Overall survival
Time Frame: 6 months
6 months
Progression-Free Survival
Time Frame: 12 months
12 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 1 month
1 month
Response Rate
Time Frame: 9 months
9 months
Overall survival
Time Frame: 9 months
9 months
Progression-Free Survival
Time Frame: 6 months
6 months
Progression-Free Survival
Time Frame: 9 months
9 months
Progression-Free Survival
Time Frame: 18 months
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intergroupe Francophone de Cancerologie Thoracique

Investigators

  • Principal Investigator: Alexis CORTOT, MD, PhD, CHRU, Lille
  • Principal Investigator: Jacques CADRANEL, MD, PhD, AP-HP Hôpital Tenon, Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2016

Primary Completion (ACTUAL)

February 1, 2019

Study Completion (ACTUAL)

April 7, 2021

Study Registration Dates

First Submitted

November 30, 2015

First Submitted That Met QC Criteria

March 22, 2016

First Posted (ESTIMATE)

March 23, 2016

Study Record Updates

Last Update Posted (ACTUAL)

August 11, 2022

Last Update Submitted That Met QC Criteria

August 9, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IFCT-1503

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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