Ignite Creation Date:
2024-05-06 @ 7:22 PM
Last Modification Date:
2024-10-26 @ 3:05 PM
Study NCT ID:
NCT05988697
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-10-12
First Post:
2023-08-04
Brief Title:
Evaluate the Efficacy and Safety of Aspirin in Combination With Trametinib and Dabrafenib
Sponsor:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Organization:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study Overview
Official Title:
An Observational Phase II Study to Evaluate the Efficacy and Safety of Aspirin in Combination With Trametinib and Dabrafenib in Advanced Non-small Cell Lung Cancer Patients With BRAF V600E Mutation
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-10
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:
None
Brief 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 15 to 35 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 didnt get a better clinical benefits of chemotherapy and immunotherapy and the progression free survival PFS of chemotherapy is only 1542 months The PFS of patients with BRAF-mutated NSCLC treated with immune checkpoint inhibitors was only 31 to 53 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 330 632 and 640 and PFS were 55 97 and 146 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 BRAFMEK 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 NRASKRAS 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 213 months which was significantly longer than the median PFS of 116 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 323 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 mgtablet 1 tablettime 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
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 213 months which was significantly longer than the median PFS of 116 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 323 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 mgtablet 1 tablettime 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
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