Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06577194
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-27
Brief Title:
A Single-Center Single-Arm Study of Neoadjuvant Short-Course Radiotherapy Concurrent With IL-2 Followed by Sequential Immunotherapy With CAPOX Combined With PD-1 Antibody and IL-2 for Locally Advanced Rectal Cancer
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Single-Center Single-Arm Study of Neoadjuvant Short-Course Radiotherapy Concurrent With IL-2 Followed by Sequential Immunotherapy With CAPOX Combined With PD-1 Antibody and IL-2 for Locally Advanced Rectal Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
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:
None
Brief Summary:
A Single-Center Single-Arm Study of Neoadjuvant Short-Course Radiotherapy Concurrent with IL-2 Followed by Sequential Immunotherapy with CAPOX Combined with PD-1 antibody and IL-2 for Locally Advanced Rectal Cancer
Detailed Description:
Globally there are around 732000 new cases of rectal cancer annually with locally advanced rectal cancer T3-4 or N comprising a significant proportion The current NCCN guidelines recommend neoadjuvant chemoradiotherapy followed by total mesorectal excision TME and adjuvant chemotherapy which has significantly reduced local recurrence rates from over 30 to less than 10 However challenges such as low rates of functional sphincter preservation high incidence of distant metastasis and limited long-term survival benefits persist In response total neoadjuvant therapy TNT-completing all chemotherapy and radiotherapy before surgery-has emerged as a strategy to improve outcomes Yet TNT may not be suitable for all patients due to the risk of overtreatment and associated toxicities
Immunotherapy including adoptive cell transfer ACT and immune checkpoint blockade ICB offers new therapeutic avenues for locally advanced rectal cancer However most colorectal cancer patients show limited responses to immunotherapy For example ACT has shown suboptimal results due to poor T-cell infiltration in tumors and only a small subset of patients benefit from immune checkpoint inhibitors ICIs While PD-1PD-L1 inhibitors are effective in mismatch repair-deficient dMMR or microsatellite instability-high MSI-H colorectal cancer MSI-H tumors account for less than 5 of rectal cancer cases Consequently most patients with microsatellite-stable MSS tumors gain minimal benefit from monotherapy
Immunotherapy resistance in MSS colorectal cancer is attributed to low tumor mutational burden poor T-cell infiltration and an immunosuppressive tumor microenvironment iTME Strategies to enhance local immune cell infiltration and reverse the iTME are crucial for improving immunotherapy efficacy in these cases For instance radiotherapy can synergize with immunotherapy by releasing tumor antigens and reshaping the immune environment to boost antitumor responses Studies like UNION and TORCH have shown promising results by combining neoadjuvant chemoradiotherapy with anti-PD-1 immunotherapy in pMMRMSS locally advanced rectal cancer patients
Interleukin-2 IL-2 plays a critical role in immune regulation promoting T-cell growth and differentiation and enhancing cytotoxic T lymphocyte CTL and natural killer NK cell activity High-dose IL-2 therapy has been used to treat malignant melanoma and renal cell carcinoma leading to long-term survival in about 15 of patients However this approach is limited by severe side effects such as hypotension and capillary leak syndrome Current research focuses on improving IL-2 efficacy at low doses including developing IL-2 variants with enhanced selectivity to avoid regulatory T cell Treg activation Additionally combining IL-2 with other treatments has shown significant clinical benefits For example in chronic lymphocytic choriomeningitis virus infection LCMV PD-1 and IL-2 combination therapy demonstrated superior efficacy compared to monotherapy Preclinical studies in tumors also showed that PD-1IL-2 combination therapy reversed terminal T-cell exhaustion generating effector CD8 T cells with enhanced profiles
Based on these findings combining IL-2 with anti-PD-1 therapy provides a strong foundation for clinical trials in locally advanced rectal cancer specifically using neoadjuvant short-course radiotherapy combined with IL-2 followed by CAPOX PD-1 monoclonal antibodies and IL-2
Immunotherapy including adoptive cell transfer ACT and immune checkpoint blockade ICB offers new therapeutic avenues for locally advanced rectal cancer However most colorectal cancer patients show limited responses to immunotherapy For example ACT has shown suboptimal results due to poor T-cell infiltration in tumors and only a small subset of patients benefit from immune checkpoint inhibitors ICIs While PD-1PD-L1 inhibitors are effective in mismatch repair-deficient dMMR or microsatellite instability-high MSI-H colorectal cancer MSI-H tumors account for less than 5 of rectal cancer cases Consequently most patients with microsatellite-stable MSS tumors gain minimal benefit from monotherapy
Immunotherapy resistance in MSS colorectal cancer is attributed to low tumor mutational burden poor T-cell infiltration and an immunosuppressive tumor microenvironment iTME Strategies to enhance local immune cell infiltration and reverse the iTME are crucial for improving immunotherapy efficacy in these cases For instance radiotherapy can synergize with immunotherapy by releasing tumor antigens and reshaping the immune environment to boost antitumor responses Studies like UNION and TORCH have shown promising results by combining neoadjuvant chemoradiotherapy with anti-PD-1 immunotherapy in pMMRMSS locally advanced rectal cancer patients
Interleukin-2 IL-2 plays a critical role in immune regulation promoting T-cell growth and differentiation and enhancing cytotoxic T lymphocyte CTL and natural killer NK cell activity High-dose IL-2 therapy has been used to treat malignant melanoma and renal cell carcinoma leading to long-term survival in about 15 of patients However this approach is limited by severe side effects such as hypotension and capillary leak syndrome Current research focuses on improving IL-2 efficacy at low doses including developing IL-2 variants with enhanced selectivity to avoid regulatory T cell Treg activation Additionally combining IL-2 with other treatments has shown significant clinical benefits For example in chronic lymphocytic choriomeningitis virus infection LCMV PD-1 and IL-2 combination therapy demonstrated superior efficacy compared to monotherapy Preclinical studies in tumors also showed that PD-1IL-2 combination therapy reversed terminal T-cell exhaustion generating effector CD8 T cells with enhanced profiles
Based on these findings combining IL-2 with anti-PD-1 therapy provides a strong foundation for clinical trials in locally advanced rectal cancer specifically using neoadjuvant short-course radiotherapy combined with IL-2 followed by CAPOX PD-1 monoclonal antibodies and IL-2
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