Trial Title:
Evaluate the Efficacy and Safety of Aspirin in Combination With Trametinib and Dabrafenib
NCT ID:
NCT05988697
Condition:
NSCLC
BRAF V600E Mutation
Advanced Cancer
Stage IIIB NSCLC
Stage IV NSCLC
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Trametinib
Dabrafenib
Conditions: Keywords:
NSCLC
Asprin
Dabrafenib
Trametinib
PFS
BRAF V600E mutation
Study type:
Observational
Overall status:
Not yet recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Drug
Intervention name:
Combind asprin with Trametinib and Dabrafenib
Description:
Treatment drug: Dabrafenib 150 mg BID, Trametinib 2 mg QD, Aspirin 100 mg/tablet, 1
tablet/time, QD
Arm group label:
Observation group
Summary:
The purpose of this study is to observe the safety and efficacy of Aspirin combined with
Trametinib and Dalafenib in the treatment of advanced BRAF V600E mutated non-small cell
lung cancer (NSCLC)
Detailed description:
lung cancer is the leading cause of morbidity and mortality in China, and non-small cell
lung cancer (NSCLC) accounts for about 85% of all lung cancers. The incidence of V-Raf
murine sarcoma viral oncogene homolog B1 (BRAF) mutations in NSCLC is 1.5% to 3.5%, and
BRAF V600 accounts for about 30-50% of all BRAF mutations, among them, V600E mutation is
the most common . NSCLC patients with BRAF V600 mutation have poor prognosis and shorter
overall survival (OS). In terms of drug therapy for these patients didn't get a better
clinical benefits of chemotherapy and immunotherapy, and the progression free survival
(PFS) of chemotherapy is only 1.5~4.2 months . The PFS of patients with BRAF-mutated
NSCLC treated with immune checkpoint inhibitors was only 3.1 to 5.3 months . In recent
years, the application of targeted therapy has brought new hope for patients with lung
cancer BRAF mutation. In three cohorts of the Phase II clinical trial BRF113928, the BRAF
inhibitor darafenib, was demonstrated has a significant efficacy as a single agent in
treated patients with BRAF V600E mutation (cohort A), combined with mitogen-activated
protein kinase (MAPK) kinase (MEK) inhibitor trametinib in treated patients (cohort B),
and combined with trametinib in treated patients (cohort C), respectively. Objective
response rates (ORR) were 33.0%, 63.2%, and 64.0%, and PFS were 5.5, 9.7, and 14.6
months, respectively. BRF113928 research shows that Dabrafenib combined with Trametinib
had good efficacy in the treatment of BRAFV600 mutant NSCLC patients, regardless of
whether it was used as first-line therapy or back-line therapy, and was superior to BRAF
single-agent targeted therapy. In terms of safety, the most common adverse event (AE) of
Dabrafenib combined with Trametinib was fever. In cohort B and cohort C, the incidence of
fever of all grades was 46% and 64%, respectively, but most of them were grade , while
the incidence of grade 3-4 AE was relatively low, 2% and 11%. In general, it is safe and
controllable . The main management methods for fever AE caused by Dabrafenib combined
with Trametinib as follows: after the first occurrence of fever syndrome, the patient
should stop taking both drugs and immediately start oral antipyretic therapy. After the
fever, it is still recommended to continue the drug for 3 days before stopping the fever
treatment. The selection and usage of related antipyretic drugs should be comprehensively
evaluated by doctors, and the options include non-steroidal anti-inflammatory drugs,
acetaminophen, and anethene. At present, the latest NCCN and CSCO both regard Dabrafenib
combined with Trametinib as the preferred first-line treatment for BRAF V600E mutated
advanced NSCLC patients . In March 2023, Dabrafenib combined with Trametinib entered the
national medical insurance directory, reducing the economic burden of patients. However,
drug resistance to targeted drugs is inevitable. Studies have shown that the resistance
mechanism of BRAF/MEK inhibitors is mainly mediated by the PI3K-Akt-mtor and RAS-RAF-MEK
pathways, such as cell cycle related gene changes, PI3K-AKT pathway activation, NRAS/KRAS
mutations, etc. Drug resistance mechanism of Dabrafenib combined with Trametinib is
complicated, there are few opportunities to use targeted drugs, also lack of clear
recommendation for follow-up treatment guidelines, usually systemic treatment such as
immunotherapy and chemotherapy are adopted. How to overcome the resistance mechanism,
delay drug resistance, and further prolong the PFS and OS of patients of Dabrafenib
combined with Trametinib still need more exploration.
Previous epidemiological studies have suggested that aspirin may reduce the incidence of
certain cancers, including lung cancer. A study from the United States included 365
patients with advanced non-small cell lung cancer treated with Osimertinib, 77 of whom
were taking aspirin while taking Osimertinib. The results showed that the median PFS of
patients treated with aspirin was 21.3 months, which was significantly longer than the
median PFS of 11.6 months of patients treated with Osimertinib alone. However, the median
OS of patients treated with aspirin was lower than that of patients treated with
Osimertinib alone, which was 32.3 months. Combined with aspirin could significantly
reduce the risk of death of patients by 44%, suggesting that EGFR-TKI combined with
aspirin could improve the patients' PFS and reduce the risk of death and bleeding events.
And the same as the targeted drugs, Dabrafenib who joint Trametinib whether can combine
with aspirin? How safe is it? Can the combination of aspirin with Dabrafenib and
Trametinib improve the PFS and OS of patients? Aspirin has antipyretic and analgesic
effects, while one of the most common adverse reactions of Dabrafenib combined with
Trametinib is fever. Can the combination of Dabrafenib combined with Trametinib reduce
the occurrence of adverse events of fever? At present, in the field of lung cancer, there
is no literature report on aspirin combined with Dabrafenib and Trametinib in the
treatment of BRAF V600E mutated advanced NSCLC. In order to solve the above problem,
further improve the BRAF V600E mutations in NSCLC patients with long-term survival, we
proposed the observational phase II study to evaluate the efficacy and safety of aspirin
combined with Dabrafenib and Trametinib in advanced NSCLC with BRAF V600E mutation.
Primary Objectives: To determine the progression-free survival time (PFS) of aspirin
combined with Dabrafenib and Trametinib;
Secondary Objectives:
A, To determine the 3 year Overall Survival (OS) in the aspirin combined with Dabrafenib
and Trametinib; B, To observe the Objective Response Rate (ORR) of aspirin combined with
Dabrafenib and Trametinib; C, To observe the Disease Control Rate (DCR) in aspirin
combined with Dabrafenib and Trametinib; D, To observe the fever-reducing rate of aspirin
combined with Dabrafenib and DabrafenibTrametinib E, To observe the risk of coronary
events in patients with aspirin combined with Dabrafenib and Trametinib.
Subjects were treated with aspirin in combination with trametinib and dalafenib. The
subject will be observed on the drug for 36 months, unless the subject develops tumor
progression (deterioration) or a toxic reaction that is difficult to tolerate.
Treatment drug: Dabrafenib 150 mg BID, Trametinib 2 mg QD, Aspirin 100 mg/tablet, 1
tablet/time, QD.
Dabrafenib or trametinib should be interrupted or adjusted in time if a participant
developed toxicity during treatment. In case of severe drug toxicity, the participant
must discontinue the drug.. If the subject develops therapeutic toxicity of Asprin during
the administration, the investigator shall interrupt or adjust the dose of aspirin in a
timely manner. If serious drug toxicity occurs, the subject must stop taking the drug.
Criteria for eligibility:
Study pop:
This study is aimed at patients with advanced non-small cell lung cancer with BRAF V600E
mutation in primary stage IIIB-IV. Dabrafenib and Trametinib are proposed for the
treatment of advanced lung cancer
Sampling method:
Probability Sample
Criteria:
Inclusion Criteria:
1. Inoperable stage IIIB-IV patients with non-small cell lung cancer;
2. BRAF V600E mutation;
3. Dabrafenib and Trametinib are planned for treatment, and the survival period is
expected to be more than 3 months;
4. ECOG PS 0/1;
5. The diameter of the primary lesion should be at least 1cm;
6. Previous or current aspirin treatment was allowed
Exclusion Criteria:
1. The patient is currently receiving other anticoagulant therapy;
2. The patient was previously treated with systemic anti-NSCLC;
3. The patient had other positive driver mutations, including EGFR, ALK, ROS1, MET14,
RET, etc.
4. The patient had contraindications for dalafenib or trametinib and aspirin use;
5. Patients who refused follow-up visits;
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
November 1, 2023
Completion date:
April 1, 2027
Lead sponsor:
Agency:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Agency class:
Other
Source:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05988697
