Ignite Creation Date:
2024-05-06 @ 8:27 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06394791
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-01
First Post:
2024-04-29
Brief Title:
Evaluation of The Efficacy And Safety of PD-1 IL-2 Combined With Capox Treatment After Loop Colostomy Surgery in Left-sided Colorectal Cancer Patients Complicating Acute Obstruction
Sponsor:
The First Affiliated Hospital with Nanjing Medical University
Organization:
The First Affiliated Hospital with Nanjing Medical University
Study Overview
Official Title:
Evaluation of The Efficacy And Safety of Tislelizumab PD-1 Monoclonal Antibody IL-2 Combined With Capox Treatment Following Loop Colostomy Surgery in Left-sided Colorectal Cancer Patients Complicating Acute Obstruction
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
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:
Evaluation of The Efficacy And Safety of Tislelizumab PD-1 Monoclonal Antibody IL-2 Combined with Capox Treatment Following Loop Colostomy Surgery in Left-sided Colorectal Cancer Patients Complicating Acute Obstruction
Detailed Description:
Colorectal cancer CRC is the second leading cause of tumor-related deaths globally with approximately 40-50 of CRC patients dying from distant metastasis Current treatments for CRC primarily include surgery chemotherapy and targeted therapy such as monoclonal antibodies against vascular endothelial growth factor VEGF and epidermal growth factor receptor EGFR However due to resistance to chemotherapy and targeted therapy local recurrence or distant metastasis of the tumor the overall 5-year survival rate for CRC remains low Therefore there is an urgent need to develop new treatment methods to improve the prognosis of patients with advanced CRC The emergence of immunotherapy including adoptive cell transfer therapy ACT and immune checkpoint blockade ICB has provided new avenues for the treatment of advanced CRC However most CRC patients have limited responses to immunotherapy For immune checkpoint inhibitors ICIs only a minority 15 of patients with mismatch repair deficiency or high microsatellite instability dMMRMSIH exhibit significant clinical remission In contrast most patients with proficient mismatch repair or microsatellite stability pMMRMSS have almost no response to ICIs In these populations low tumor mutation burden TMB and insufficient immunogenicity leading to inadequate immune cell infiltration are considered major mechanisms of resistance to immunotherapy Therefore how to enhance immune cell infiltration and improve the therapeutic effect of immunotherapy in low-responsive CRC remains a critical issue
In colorectal cancer the incidence of tumor-associated intestinal obstruction ranges from 8 to 30 with most obstructions located in the left colon sigmoid colon and upper rectum The most common treatment is emergency surgery to relieve obstruction as soon as possible However the risk of anastomotic fistula and the incidence of complications and mortality are relatively high for emergency surgery with proximal and distal bowel anastomosis Therefore these patients usually opt for colostomy staged surgery treatment Hartmann39s procedure Additionally due to unstable vital signs bowel dilation and bowel and mesenteric edema comprehensive lymph node dissection and mesenteric resection are limited which may adversely affect the prognosis of the patient In recent years many studies have reported on 34stent combined with staged surgery34 as a treatment method for left-sided colon cancer with obstruction but some views believe that stents have the potential risk of compressing the tumor causing micro-perforation of the intestinal wall leading to local implantation and increasing the possibility of tumor cell vascular infiltration Although the waiting period after stent placement can introduce neoadjuvant therapy existing evidence has not yet proven that stent combined with chemotherapy can effectively downstage the tumor However the delay in surgery caused by preoperative chemotherapy does not pose a risk of tumor progression Current research indicates that acute intestinal obstruction in malignant tumors of the colon exacerbates the body39s stress response including significant accumulation of inflammatory factors such as TNF-α IL6 throughout the body Moreover from a pathophysiological perspective acute obstruction of colorectal cancer leads to local tissue edema and enhanced inflammatory response and the tumor tissue may release tumor antigens due to ischemia and necrosis further inducing the body39s immune response These potential mechanisms provide theoretical support for preoperative neoadjuvant chemotherapy combined with immunotherapy for these patients
In immunotherapy the PD-1 inhibition pathway plays a central role in regulating immune cell exhaustion however most colorectal cancer patients have limited response to PD-1 monotherapy hence combining PD1 with other immune-enhancing drugs is hoped to address the above challenges Currently some combination therapies have made progress in animal models and are applied in clinical research Interleukin-2 IL-2 is a promising candidate drug synergizing with PD-1 blockade to exert anti-cancer effects In our phase I clinical study Capox combined with PD1IL2 significantly improved the clinical complete remission rate of neoadjuvant therapy for locally advanced rectal cancer
In colorectal cancer the incidence of tumor-associated intestinal obstruction ranges from 8 to 30 with most obstructions located in the left colon sigmoid colon and upper rectum The most common treatment is emergency surgery to relieve obstruction as soon as possible However the risk of anastomotic fistula and the incidence of complications and mortality are relatively high for emergency surgery with proximal and distal bowel anastomosis Therefore these patients usually opt for colostomy staged surgery treatment Hartmann39s procedure Additionally due to unstable vital signs bowel dilation and bowel and mesenteric edema comprehensive lymph node dissection and mesenteric resection are limited which may adversely affect the prognosis of the patient In recent years many studies have reported on 34stent combined with staged surgery34 as a treatment method for left-sided colon cancer with obstruction but some views believe that stents have the potential risk of compressing the tumor causing micro-perforation of the intestinal wall leading to local implantation and increasing the possibility of tumor cell vascular infiltration Although the waiting period after stent placement can introduce neoadjuvant therapy existing evidence has not yet proven that stent combined with chemotherapy can effectively downstage the tumor However the delay in surgery caused by preoperative chemotherapy does not pose a risk of tumor progression Current research indicates that acute intestinal obstruction in malignant tumors of the colon exacerbates the body39s stress response including significant accumulation of inflammatory factors such as TNF-α IL6 throughout the body Moreover from a pathophysiological perspective acute obstruction of colorectal cancer leads to local tissue edema and enhanced inflammatory response and the tumor tissue may release tumor antigens due to ischemia and necrosis further inducing the body39s immune response These potential mechanisms provide theoretical support for preoperative neoadjuvant chemotherapy combined with immunotherapy for these patients
In immunotherapy the PD-1 inhibition pathway plays a central role in regulating immune cell exhaustion however most colorectal cancer patients have limited response to PD-1 monotherapy hence combining PD1 with other immune-enhancing drugs is hoped to address the above challenges Currently some combination therapies have made progress in animal models and are applied in clinical research Interleukin-2 IL-2 is a promising candidate drug synergizing with PD-1 blockade to exert anti-cancer effects In our phase I clinical study Capox combined with PD1IL2 significantly improved the clinical complete remission rate of neoadjuvant therapy for locally advanced rectal cancer
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