Ignite Creation Date:
2024-07-17 @ 10:46 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06469060
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-01
First Post:
2024-06-16
Brief Title:
Neoadjuvant Immunochemotherapy for Adenocarcinoma of the Esophagogastric Junction
Sponsor:
Shanghai Chest Hospital
Organization:
Shanghai Chest Hospital
Study Overview
Official Title:
Tislelizumab Combined With Chemotherapy as Neoadjuvant Regimen for AdenoCarcinoma of the Esophagogastric Junction a Single-arm Phase II Clinical Trial TRACE
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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:
TRACE
Brief Summary:
The investigators will conduct a prospective phase 2 study to evaluate the efficacy and safety of a modified neoadjuvant immunotherapy plus chemotherapy one cycle of Tislelizumab monotherapy followed by four cycles of Tislelizumab plus Docetaxel Oxaliplatin and Capecitabine in patients with locally advanced resectable adenocarcinoma of the esophagogastric junction AEG
Detailed Description:
Adenocarcinoma of the esophagogastric junction AEG has recently garnered increasing attention as a distinct type of malignancy The World Health Organization WHO defines AEG as adenocarcinoma with its center located within 5 cm above or below the esophagogastric junction crossing or abutting this junction PMID 31433515 Surgery remains the primary treatment for locally advanced AEG but numerous studies have demonstrated that multimodal therapies such as neoadjuvant chemoradiotherapy and chemotherapy can achieve better outcomes
The CROSS study PMID 22646630 established neoadjuvant chemoradiotherapy as the standard treatment for resectable esophageal and esophagogastric junction cancers This trimodal approach not only significantly increased the R0 resection rate but also improved overall survival OS The FLOT4 study PMID 30982686 compared the efficacy and safety of perioperative FLOT chemotherapy with perioperative ECF chemotherapy in treating gastric cancerAEG The study found that the R0 resection rate was significantly higher in the FLOT group compared to the ECFECX group 85 vs 78 Patients in the FLOT group had a median OS of 50 months compared to 35 months in the ECXECF group demonstrating that intensified perioperative systemic therapy enhances neoadjuvant efficacy Despite these advances the overall prognosis for locally advanced AEG remains poor with a 5-year survival rate of less than 45 Thus there is an urgent need for new treatment strategies to further improve perioperative chemotherapy outcomes for AEG
Currently immunotherapy combined with chemotherapy has become the first-line standard treatment recommendation for advanced esophageal cancerAEG CheckMate649 PMID 34102137 Rationale 305 PMID 38806195 In exploring perioperative immunotherapy for AEG results from two global Phase III randomized controlled trials KEYNOTE-585 PMID 38134948 and MATTERHORN 2023 ESMO Abstract LBA73 indicated that neoadjuvant immunotherapy combined with chemotherapy significantly increased the pathological complete response rate pCR in AEG patients compared to neoadjuvant chemotherapy alone 13 vs 2 and 17 vs 7 respectively Furthermore the neoadjuvant immunotherapy combined with chemotherapy groups did not show an increase in adverse events during the neoadjuvant period compared to the neoadjuvant chemotherapy alone groups 64 vs 63 and 58 vs 56 respectively However the improvement in overall survival prognosis remains insufficient suggesting the need to further optimize neoadjuvant immunotherapy protocols to achieve better therapeutic benefits
The way for optimizing the treatment strategy for immune-chemotherapy includes the modifications of dose drug selection number of cycles schedule and sequencing PMID 33712487 The PANDA study initiated by Dutch researchers is a single-arm Phase II clinical trial that enrolled 21 patients with resectable AEG PMID 38191613 The neoadjuvant treatment involved one induction cycle of single-agent immunotherapy atezolizumab followed by four cycles of sequential immunotherapy combined with DOC chemotherapy before surgery The postoperative pCR rate was 45 and the major pathological response MPR rate was 70 13 out of 14 MPR patients achieved disease-free survival for up to four years This study demonstrated that the initial induction with single-agent immunotherapy significantly altered the tumor immune microenvironment inducing an immune activation state that provided a critical foundation for the efficacy of subsequent sequential immunotherapy combined with chemotherapy The results suggest that an initial induction with single-agent immunotherapy prior to immunotherapy combining chemotherapy is a superior neoadjuvant immuno-chemotherapy strategy for resectable locally advanced AEG warranting further exploration and validation in larger cohorts of AEG patients
However for Asia particularly China given the large base of esophageal cancer cases and the rising incidence of esophageal adenocarcinoma exploring optimal neoadjuvant treatment strategies for resectable AEG patients in China has become a critical clinical issue
This study aims to investigate the efficacy and safety of neoadjuvant immunotherapy induction followed by sequential immune-chemotherapy in patients with locally advanced AEG
The CROSS study PMID 22646630 established neoadjuvant chemoradiotherapy as the standard treatment for resectable esophageal and esophagogastric junction cancers This trimodal approach not only significantly increased the R0 resection rate but also improved overall survival OS The FLOT4 study PMID 30982686 compared the efficacy and safety of perioperative FLOT chemotherapy with perioperative ECF chemotherapy in treating gastric cancerAEG The study found that the R0 resection rate was significantly higher in the FLOT group compared to the ECFECX group 85 vs 78 Patients in the FLOT group had a median OS of 50 months compared to 35 months in the ECXECF group demonstrating that intensified perioperative systemic therapy enhances neoadjuvant efficacy Despite these advances the overall prognosis for locally advanced AEG remains poor with a 5-year survival rate of less than 45 Thus there is an urgent need for new treatment strategies to further improve perioperative chemotherapy outcomes for AEG
Currently immunotherapy combined with chemotherapy has become the first-line standard treatment recommendation for advanced esophageal cancerAEG CheckMate649 PMID 34102137 Rationale 305 PMID 38806195 In exploring perioperative immunotherapy for AEG results from two global Phase III randomized controlled trials KEYNOTE-585 PMID 38134948 and MATTERHORN 2023 ESMO Abstract LBA73 indicated that neoadjuvant immunotherapy combined with chemotherapy significantly increased the pathological complete response rate pCR in AEG patients compared to neoadjuvant chemotherapy alone 13 vs 2 and 17 vs 7 respectively Furthermore the neoadjuvant immunotherapy combined with chemotherapy groups did not show an increase in adverse events during the neoadjuvant period compared to the neoadjuvant chemotherapy alone groups 64 vs 63 and 58 vs 56 respectively However the improvement in overall survival prognosis remains insufficient suggesting the need to further optimize neoadjuvant immunotherapy protocols to achieve better therapeutic benefits
The way for optimizing the treatment strategy for immune-chemotherapy includes the modifications of dose drug selection number of cycles schedule and sequencing PMID 33712487 The PANDA study initiated by Dutch researchers is a single-arm Phase II clinical trial that enrolled 21 patients with resectable AEG PMID 38191613 The neoadjuvant treatment involved one induction cycle of single-agent immunotherapy atezolizumab followed by four cycles of sequential immunotherapy combined with DOC chemotherapy before surgery The postoperative pCR rate was 45 and the major pathological response MPR rate was 70 13 out of 14 MPR patients achieved disease-free survival for up to four years This study demonstrated that the initial induction with single-agent immunotherapy significantly altered the tumor immune microenvironment inducing an immune activation state that provided a critical foundation for the efficacy of subsequent sequential immunotherapy combined with chemotherapy The results suggest that an initial induction with single-agent immunotherapy prior to immunotherapy combining chemotherapy is a superior neoadjuvant immuno-chemotherapy strategy for resectable locally advanced AEG warranting further exploration and validation in larger cohorts of AEG patients
However for Asia particularly China given the large base of esophageal cancer cases and the rising incidence of esophageal adenocarcinoma exploring optimal neoadjuvant treatment strategies for resectable AEG patients in China has become a critical clinical issue
This study aims to investigate the efficacy and safety of neoadjuvant immunotherapy induction followed by sequential immune-chemotherapy in patients with locally advanced AEG
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