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.
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
Drug | Synonyms | Arms |
---|
Afatinib | | Afatinib |
Cetuximab | | Afatinib + 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
Name | Type | Description | Interventions |
---|
Afatinib | Other | Afatinib 40 mg/d until progression | |
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) | |
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: | Active, not recruiting |
Lead Sponsor: | Intergroupe Francophone de Cancerologie Thoracique |
Trial Keywords
Last Updated
April 24, 2020