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

Study Overview
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Brief Summary
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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.

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

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Afatinib
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Afatinib<br>Afatinib 40 mg/d until progression | Drug: Afatinib<br> <br> |
| Experimental: Afatinib + cetuximab<br>Afatinib 40 mg/d until progression + cetuximab 500 mg/m² every 2 weeks during 6 months (beginning at D15 at 250 mg/m²) | Drug: Afatinib<br> <br> Drug: Cetuximab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Treatment Failure |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Progression-Free Survival |  | 6 months | 
| Progression-Free Survival |  | 9 months | 
| Progression-Free Survival |  | 12 months | 
| Progression-Free Survival |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR, Lung Cancer