Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06594692
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-10
Brief Title:
Node-Sparing Short-Course Radiation with CAPOX and Sintilimab for MSS Locally Advanced Colon Cancer a Randomized Prospective Multicenter Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Node-sparing Modified Short-Course Radiation Combined with CAPOX and Sintilimab for MSS Locally Advanced Colon Cancer a Randomized Prospective Multicenter Open-label Clinical Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
mRCAT-C
Brief Summary:
This study aims to evaluate the use of node-sparing short-course radiotherapy combined with chemotherapy and Sintilimab or chemotherapy alone as neoadjuvant therapy for MSS-type locally advanced colon cancer The goal is to explore the efficacy and safety of combining node-sparing short-course radiotherapy with chemotherapy and immunotherapy in the neoadjuvant setting for MSS-type locally advanced colon cancer while also investigating the specific role of regional lymph nodes in tumor immunotherapy
Detailed Description:
Colorectal cancer is currently one of the most common malignant tumors in China According to the latest data released by the National Cancer Center it ranks second in incidence and fourth in mortality among all cancer types Statistics indicate that approximately 50 of colon cancer patients in China are in stages II-III Currently adjuvant chemotherapy regimens containing oxaliplatin and 5-fluorouracil are the standard treatment for stage III and high-risk stage II colon cancer patients However under standard treatment protocols the 5-year disease-free survival DFS rate for stage III colon cancer is less than 64 with a recurrence rate exceeding 20 Patients with higher T and N stages face a significantly increased risk of recurrence severely impacting survival rates and imposing a substantial burden on both the healthcare system and society
Neoadjuvant chemotherapy which is administered before surgery offers several theoretical advantages including shrinking the primary tumor to improve surgical resection rates reducing intraoperative tumor cell spread and eliminating micrometastases and subclinical lesions to lower the risk of postoperative metastasis However data on neoadjuvant chemotherapy for locally advanced colon cancer remains limited The FOxTROT study found that preoperative neoadjuvant chemotherapy significantly reduced the 2-year recurrence rate for locally advanced colon cancer achieved tumor downstaging and provided a 4 pathological complete response pCR rate This study also demonstrated a strong correlation between pathological response to neoadjuvant therapy and recurrence risk with patients achieving pCR or major pathological response mPR having significantly lower recurrence rates
Recent studies have shown that combining immunotherapy with radiotherapy has a synergistic effect even in MSS-type colorectal cancer patients Radiotherapy can induce immunogenic cell death releasing tumor-associated antigens and enhancing the function of dendritic cells thereby increasing T-cell infiltration Moreover chemotherapy can alter the tumor microenvironment promote angiogenesis and improve oxygen distribution further enhancing the efficacy of radiotherapy One prospective phase II clinical trial involving locally advanced rectal cancer patients showed promising results with a pCR rate of 462 in patients with proficient mismatch repair pMMR suggesting a favorable response to neoadjuvant therapy
Lymph nodes as secondary lymphoid organs play a crucial role in tumor diagnosis and treatment Recent preclinical studies have shown that tumor-draining lymph nodes TDLNs are essential in antigen activation and effector T-cell differentiation On the other hand tertiary lymphoid structures TLS which are organized immune cell aggregates formed in non-lymphoid tissues have been associated with improved prognosis in cancer patients However the role of TDLNs in immunotherapy remains underexplored
Based on these findings the research team hypothesizes that tumor-draining lymph nodes play a positive role in immunotherapy response and sparing these nodes during radiotherapy may enhance the efficacy of immunotherapy for MSS-type colorectal cancer The team previously conducted a phase II clinical study NCT04503694 investigating the safety and efficacy of node-sparing short-course radiotherapy combined with CAPOX chemotherapy and PD-1 inhibitors in MSS-type locally advanced rectal cancer Results showed a 100 response rate to neoadjuvant therapy with a pCR rate of 788 and a major pathological response mPR rate of 91 while maintaining a high rate of organ preservation
Given the high recurrence rates and treatment challenges associated with locally advanced colon cancer and building on the promising results of previous studies the research team intends to conduct the mRCAT-C study This study aims to explore the clinical efficacy and safety of a node-sparing short-course radiotherapy combined with immunotherapy as a neoadjuvant treatment for MSS-type locally advanced colon cancer
Neoadjuvant chemotherapy which is administered before surgery offers several theoretical advantages including shrinking the primary tumor to improve surgical resection rates reducing intraoperative tumor cell spread and eliminating micrometastases and subclinical lesions to lower the risk of postoperative metastasis However data on neoadjuvant chemotherapy for locally advanced colon cancer remains limited The FOxTROT study found that preoperative neoadjuvant chemotherapy significantly reduced the 2-year recurrence rate for locally advanced colon cancer achieved tumor downstaging and provided a 4 pathological complete response pCR rate This study also demonstrated a strong correlation between pathological response to neoadjuvant therapy and recurrence risk with patients achieving pCR or major pathological response mPR having significantly lower recurrence rates
Recent studies have shown that combining immunotherapy with radiotherapy has a synergistic effect even in MSS-type colorectal cancer patients Radiotherapy can induce immunogenic cell death releasing tumor-associated antigens and enhancing the function of dendritic cells thereby increasing T-cell infiltration Moreover chemotherapy can alter the tumor microenvironment promote angiogenesis and improve oxygen distribution further enhancing the efficacy of radiotherapy One prospective phase II clinical trial involving locally advanced rectal cancer patients showed promising results with a pCR rate of 462 in patients with proficient mismatch repair pMMR suggesting a favorable response to neoadjuvant therapy
Lymph nodes as secondary lymphoid organs play a crucial role in tumor diagnosis and treatment Recent preclinical studies have shown that tumor-draining lymph nodes TDLNs are essential in antigen activation and effector T-cell differentiation On the other hand tertiary lymphoid structures TLS which are organized immune cell aggregates formed in non-lymphoid tissues have been associated with improved prognosis in cancer patients However the role of TDLNs in immunotherapy remains underexplored
Based on these findings the research team hypothesizes that tumor-draining lymph nodes play a positive role in immunotherapy response and sparing these nodes during radiotherapy may enhance the efficacy of immunotherapy for MSS-type colorectal cancer The team previously conducted a phase II clinical study NCT04503694 investigating the safety and efficacy of node-sparing short-course radiotherapy combined with CAPOX chemotherapy and PD-1 inhibitors in MSS-type locally advanced rectal cancer Results showed a 100 response rate to neoadjuvant therapy with a pCR rate of 788 and a major pathological response mPR rate of 91 while maintaining a high rate of organ preservation
Given the high recurrence rates and treatment challenges associated with locally advanced colon cancer and building on the promising results of previous studies the research team intends to conduct the mRCAT-C study This study aims to explore the clinical efficacy and safety of a node-sparing short-course radiotherapy combined with immunotherapy as a neoadjuvant treatment for MSS-type locally advanced colon cancer
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None