Ignite Creation Date:
2024-05-06 @ 3:50 PM
Last Modification Date:
2024-10-26 @ 1:58 PM
Study NCT ID:
NCT04775095
Status:
COMPLETED
Last Update Posted:
2023-01-06
First Post:
2021-02-24
Brief Title:
BRAF V600-mutated Lung Carcinoma Treated With the Combination of Dabrafenib-trametinib a Retrospective Evaluation
Sponsor:
Intergroupe Francophone de Cancerologie Thoracique
Organization:
Intergroupe Francophone de Cancerologie Thoracique
Study Overview
Official Title:
BRAF V600-mutated Lung Carcinoma Treated With the Combination of Dabrafenib-trametinib a Retrospective Evaluation Secondary Data Use Study of Dabrafenib-Trametinib in Real Life for Non-Small Cell Lung Cancer With a BRAF V600 Mutation
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BLaDE
Brief Summary:
BLaDE cohort will evaluate overall survival OS real world progression-free survival PFS best response and duration of treatment in patients with advanced metastatic Non-Small Cell Lung Cancer NSCLC harboring BRAF V600E or non E mutation who received dabrafeninb-trametinib combination or not Subsequent or previous treatments treatments delivered after or before dabrafeninb-trametinib combination will be recorded Those outcomes will be correlated to clinical pathological and radiological characteristics of patients
Detailed Description:
The braf gene V Raf murine sarcoma viral oncogene homolog long arm of chromosome 7q3 codes for a protein serine threonine kinase which regulates the signaling pathway RAS - RAF - MEK - ERK playing an important role in the proliferation processes cell survival angiogenesis cell invasion and migration
When activated by mutations BRAF phosphorylates MEK to promote cell growth proliferation and survival In non-small cell lung cancer NSCLC BRAF mutations are found in 1-2 of cases BRAF mutations are distinguished by kinase activity and their signaling via the mitogen-activated kinase MAPK pathway BRAF V600 mutations class I signal as monomers with or without activated RAS BRAF non-V600 are classified as either class II that signal as dimmers when RAS as activated or class III with impaired kinase activity but increased MAPK pathway signaling The most frequent mutation in NSCLC 50 of cases is the V600E mutation glutamate valine substitution codon 600 of exon 15 which is activating others mutations G469A and D594G respectively 39 and 11 of cases One phase II trial demonstrated that the dabrafenib-trametinib combination had significant anti-tumor activity in terms of response rate PFS in patients with a NSCLC with the BRAF V600E mutation pretreated or not In this multicentre non-randomized phase II open label study a dabrafenib-trametinib combination was tested in 59 previously treated patients with metastatic stage IV BRAF V600E mutated NSCLC with documented progression after at least one prior platinum based chemotherapy Overall response rate ORR was 632 95 CI 493 to 756 median PFS was 97 months 95CI 69-196 In the cohort of patients previously untreated n36 and treated with first line dabrafenib-trametinib combination the investigator-assessed confirmed ORR was 64 95 CI 46-79 the median investigator assessed PFS was 109 months 95CI7-166 and the 6 month-PFS was 72 53-84 respectively
At the last ASCO conference 2020 the data have been updated In cohorts of untreated and previously treated patients the ORR was 639 95CI 462-792 and 684 95CI 548 801 median PFS 108 months 95CI 70-145 and 102 months 95CI 69-167 Median OS was 173 months 95 CI 123-402 3 years OS 40 and 182 months 95 CI 143-286 3 years OS 33 with 1436 and 1157 patients alive in treatment naïve and pretreated patients respectively
The dabrafenib-trametinib combination had European authorization since 2017 In January 2020 the French Transparency Committee validated its possible use in second line in current practice after failure of a first therapeutic line whatever its nature but only for BRAF V600E mutations Clinical outcomes data on BRAF-mutated V600 NSCLC patients treated in routine practice by dabrafenib-trametinib combination is limited with only retrospective studies including few patients
The primary objective of this retrospective multicenter observational study is to describe in real world the characteristics and evolution of NSCLC patients with a BRAF V600 E mutation treated with the dabrafenib-trametinib combination regardless of the line of treatment Also this retrospective multicenter observational will describe in real world the characteristics treatment and evolution of NSCLC patients with a BRAF V600 non E mutation
When activated by mutations BRAF phosphorylates MEK to promote cell growth proliferation and survival In non-small cell lung cancer NSCLC BRAF mutations are found in 1-2 of cases BRAF mutations are distinguished by kinase activity and their signaling via the mitogen-activated kinase MAPK pathway BRAF V600 mutations class I signal as monomers with or without activated RAS BRAF non-V600 are classified as either class II that signal as dimmers when RAS as activated or class III with impaired kinase activity but increased MAPK pathway signaling The most frequent mutation in NSCLC 50 of cases is the V600E mutation glutamate valine substitution codon 600 of exon 15 which is activating others mutations G469A and D594G respectively 39 and 11 of cases One phase II trial demonstrated that the dabrafenib-trametinib combination had significant anti-tumor activity in terms of response rate PFS in patients with a NSCLC with the BRAF V600E mutation pretreated or not In this multicentre non-randomized phase II open label study a dabrafenib-trametinib combination was tested in 59 previously treated patients with metastatic stage IV BRAF V600E mutated NSCLC with documented progression after at least one prior platinum based chemotherapy Overall response rate ORR was 632 95 CI 493 to 756 median PFS was 97 months 95CI 69-196 In the cohort of patients previously untreated n36 and treated with first line dabrafenib-trametinib combination the investigator-assessed confirmed ORR was 64 95 CI 46-79 the median investigator assessed PFS was 109 months 95CI7-166 and the 6 month-PFS was 72 53-84 respectively
At the last ASCO conference 2020 the data have been updated In cohorts of untreated and previously treated patients the ORR was 639 95CI 462-792 and 684 95CI 548 801 median PFS 108 months 95CI 70-145 and 102 months 95CI 69-167 Median OS was 173 months 95 CI 123-402 3 years OS 40 and 182 months 95 CI 143-286 3 years OS 33 with 1436 and 1157 patients alive in treatment naïve and pretreated patients respectively
The dabrafenib-trametinib combination had European authorization since 2017 In January 2020 the French Transparency Committee validated its possible use in second line in current practice after failure of a first therapeutic line whatever its nature but only for BRAF V600E mutations Clinical outcomes data on BRAF-mutated V600 NSCLC patients treated in routine practice by dabrafenib-trametinib combination is limited with only retrospective studies including few patients
The primary objective of this retrospective multicenter observational study is to describe in real world the characteristics and evolution of NSCLC patients with a BRAF V600 E mutation treated with the dabrafenib-trametinib combination regardless of the line of treatment Also this retrospective multicenter observational will describe in real world the characteristics treatment and evolution of NSCLC patients with a BRAF V600 non E mutation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None