Clinical Trials /

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

NCT02716311

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: IFCT-1503
  • NCT ID: NCT02716311

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
AfatinibAfatinib
CetuximabAfatinib + cetuximab

Purpose

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 Arms

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

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to Treatment Failure
Time Frame:9 months
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Intergroupe Francophone de Cancerologie Thoracique

Trial Keywords

  • EGFR
  • Lung Cancer

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