Combination of Cetuximab With Afatinib for Patient With EGFR Mutated Lung Cancer

Phase 2

Completed

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: Afatinib; Drug: Cetuximab

• Registration Number: NCT02716311
• Lead Sponsor: Intergroupe Francophone de Cancerologie Thoracique

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-30
• Study First Submitted QC: 2016-03-22
• Study First Posted: 2016-03-23
• Study Start: 2016-05
• Primary Completion: 2019-02
• Study Completion: 2021-04-07
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-09
• Last Update Posted: 2022-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 118

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Time to Treatment Failure	9 months

Secondary Outcome Measures

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

Trial Locations

Locations (33)

Centre Hospitalier du Pays d'Aix; 🇫🇷 Aix-en-Provence, France

Clinique de L'Europe; 🇫🇷 Amiens, France

Angers - CHU; 🇫🇷 Angers, France

Annecy - CH; 🇫🇷 Annecy, France

Bordeaux - Institut Bergonié; 🇫🇷 Bordeaux, France

Bordeaux - Polyclinique Nord; 🇫🇷 Bordeaux, France

Boulogne - Ambroise Paré; 🇫🇷 Boulogne-Billancourt, France

Clermont-Ferrand - CHU; 🇫🇷 Clermont-Ferrand, France

CH; 🇫🇷 Colmar, France

CHRU Grenoble; 🇫🇷 Grenoble, France

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