Ignite Creation Date:
2025-12-25 @ 2:01 AM
Ignite Modification Date:
2026-01-06 @ 2:36 AM
Study NCT ID:
NCT06469060
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-01
First Post:
2024-06-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Neoadjuvant Immunochemotherapy for Adenocarcinoma of the Esophagogastric Junction
Sponsor:
Shanghai Chest Hospital
Organization:
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 cancer/AEG. The study found that the R0 resection rate was significantly higher in the FLOT group compared to the ECF/ECX group (85% vs. 78%). Patients in the FLOT group had a median OS of 50 months, compared to 35 months in the ECX/ECF 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 cancer/AEG (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 cancer/AEG. The study found that the R0 resection rate was significantly higher in the FLOT group compared to the ECF/ECX group (85% vs. 78%). Patients in the FLOT group had a median OS of 50 months, compared to 35 months in the ECX/ECF 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 cancer/AEG (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:
True
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?: