Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04775095 |
| Other study ID # |
IFCT-2004 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 8, 2021 |
| Est. completion date |
December 31, 2021 |
Study information
| Verified date |
January 2023 |
| Source |
Intergroupe Francophone de Cancerologie Thoracique |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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 63.2% (95% CI: 49.3 to
75.6%), median PFS was 9.7 months (95%CI 6.9-19.6). In the cohort of patients previously
untreated (n=36) 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 10.9 months (95CI:7-16.6) 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 63.9% (95CI 46.2-79.2) and 68.4% (95CI 54.8, 80.1),
median PFS 10.8 months (95CI 7.0-14.5) and 10.2 months (95CI: 6.9-16.7). Median OS was 17.3
months (95% CI: 12.3-40.2; 3 years OS: 40%) and 18.2 months (95% CI: 14.3-28.6; 3 years OS:
33%) with 14/36 and 11/57 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.
