Ignite Creation Date:
2024-06-16 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06446726
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-06
First Post:
2024-05-16
Brief Title:
Low-dose Radiation Combined With Neoadjuvant Immunochemotherapy for Esophageal Squamous Cell Carcinoma
Sponsor:
Sichuan University
Organization:
Sichuan University
Study Overview
Official Title:
Efficacy and Safety of Low-dose Radiation Combined With Neoadjuvant Chemotherapy and Immunotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma
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:
None
Brief Summary:
This study aims to investigate the efficacy and safety of low-dose radiation combined with neoadjuvant chemotherapy and immunotherapy in the treatment of locally advanced thoracic esophageal squamous cell carcinoma By reducing the radiation dose from 40 Gy in 20 fractions to 4 Gy in 2 fractions the goal is to lessen the adverse reactions caused by radiotherapy Additionally the study explores whether low-dose radiation therapy can promote the cross-presentation of tumor-specific antigens and increase lymphocyte infiltration into the tumor site Study also examines whether this approach can enhance tumor-specific immune responses thereby potentially improving the efficacy of immune checkpoint inhibitors
Detailed Description:
According to 2020 GLOBOCAN data esophageal cancer ranks fifth in incidence among all malignant tumors in China with new cases reaching 324000 and annual deaths at 301000 These figures indicate a significant burden of esophageal cancer in China accounting for 55 of esophageal cancer cases globally Unlike in Western countries most esophageal cancer patients in China have squamous cell carcinoma and 40 are diagnosed at an advanced stage Surgery is a key treatment for locally advanced esophageal cancer but patients may achieve better clinical outcomes if they receive neoadjuvant therapy before surgery However the prognosis for these patients remains relatively poor From 2009 to 2015 the overall 5-year relative survival rate for esophageal cancer was 214 with local tumors at 467 regional metastasis at 251 and distant metastasis at only 48
In recent years immunotherapy has shown significant survival benefits in patients with advanced esophageal cancer Immuno-chemotherapy has now become the standard first-line treatment for advanced esophageal cancer Currently the introduction of immunotherapy as neoadjuvant treatment in locally advanced esophageal cancer is a highly regarded research area Many studies are underway involving the combined application of neoadjuvant chemotherapy and immunotherapy as well as neoadjuvant chemoradiotherapy and immunotherapy Regarding safety tislelizumab is similar to foreign similar drugs mostly causing grade 1-2 adverse reactions and is within a controllable range Our centers previous research results have shown that tislelizumab can be used as a neoadjuvant immunotherapy drug for esophageal squamous cell carcinoma with good perioperative safety
It is worth noting that recent study reports indicate that the pathological complete response PCR rate of neoadjuvant chemotherapy combined with immunotherapy in small sample studies ranges from 17 to 22 showing significant heterogeneity Recently Chinese scholars published a study in the international authoritative academic journal Nature Medicine indicating that using a PD-L1 antibody for immunotherapy combined with surgery although the PCR rate was only 8 the long-term survival effect was comparable to traditional chemoradiotherapy This further proves that compared to traditional neoadjuvant chemoradiotherapy neoadjuvant immunotherapy has broad development potential However the local control effects of immunotherapy alone or combined with chemotherapy are still unsatisfactory which may affect the radical outcome of surgery and the long-term survival of patients Therefore combining more effective local treatment methods with immunotherapy is undoubtedly a more promising treatment option
Low-dose radiotherapy LDRT is generally defined as a treatment not exceeding 2 Gy per session totaling no more than 10 Gy and is considered a non-ablative treatment 13 The low toxicity of low-dose radiotherapy makes it a treatment option for those not suitable for body-targeted radiation therapy Furthermore although low-dose radiotherapy does not directly kill cancer cells it can promote tumor regression by readjusting the tumor immune microenvironment
Low-dose radiotherapy damages cell DNA causing previously hidden or difficult-to-recognize tumor antigens to be exposed on the cell surface This change promotes the cross-presentation of tumor-specific antigens increases lymphocyte infiltration into the tumor site enhances tumor-specific immune responses and further improves the efficacy of immune checkpoint inhibitors Preoperative immunotherapy can activate the patients immune system enabling it to recognize tumor antigens and establish immune memory This allows the immune system to continue to function in immune surveillance after the surgical removal of the tumor Currently the main focus of clinical research is on how to maximize the synergistic effects between different treatment modalities to achieve the best survival outcomes for patients with locally advanced esophageal cancer while minimizing treatment side effects
This study is a Phase IIA clinical trial a preliminary study of efficacy and safety This study envisions a comprehensive treatment of neoadjuvant low-dose radiotherapy combined with chemotherapy and immunotherapy chemo-immuno which by reducing the radiotherapy dose can enhance local control efficacy and reduce adverse reactions caused by the combined treatment mode Therefore it is proposed to perform neoadjuvant low-dose radiotherapy combined with chemo-immuno treatment in patients with locally advanced esophageal squamous cell carcinoma adjust the preoperative radiotherapy dose from 40 Gy20f to 4 Gy2f evaluate the efficacy and safety of this treatment mode and provide more evidence for the neoadjuvant treatment model for locally advanced esophageal cancer patients Additionally exploratory analyses of preoperative and postoperative tissue and blood samples will be conducted to understand the impact of preoperative low-dose radiotherapy combined with immunotherapy on the esophageal cancer immune microenvironment suitable biological markers will be selected to identify the optimal beneficiary group
In recent years immunotherapy has shown significant survival benefits in patients with advanced esophageal cancer Immuno-chemotherapy has now become the standard first-line treatment for advanced esophageal cancer Currently the introduction of immunotherapy as neoadjuvant treatment in locally advanced esophageal cancer is a highly regarded research area Many studies are underway involving the combined application of neoadjuvant chemotherapy and immunotherapy as well as neoadjuvant chemoradiotherapy and immunotherapy Regarding safety tislelizumab is similar to foreign similar drugs mostly causing grade 1-2 adverse reactions and is within a controllable range Our centers previous research results have shown that tislelizumab can be used as a neoadjuvant immunotherapy drug for esophageal squamous cell carcinoma with good perioperative safety
It is worth noting that recent study reports indicate that the pathological complete response PCR rate of neoadjuvant chemotherapy combined with immunotherapy in small sample studies ranges from 17 to 22 showing significant heterogeneity Recently Chinese scholars published a study in the international authoritative academic journal Nature Medicine indicating that using a PD-L1 antibody for immunotherapy combined with surgery although the PCR rate was only 8 the long-term survival effect was comparable to traditional chemoradiotherapy This further proves that compared to traditional neoadjuvant chemoradiotherapy neoadjuvant immunotherapy has broad development potential However the local control effects of immunotherapy alone or combined with chemotherapy are still unsatisfactory which may affect the radical outcome of surgery and the long-term survival of patients Therefore combining more effective local treatment methods with immunotherapy is undoubtedly a more promising treatment option
Low-dose radiotherapy LDRT is generally defined as a treatment not exceeding 2 Gy per session totaling no more than 10 Gy and is considered a non-ablative treatment 13 The low toxicity of low-dose radiotherapy makes it a treatment option for those not suitable for body-targeted radiation therapy Furthermore although low-dose radiotherapy does not directly kill cancer cells it can promote tumor regression by readjusting the tumor immune microenvironment
Low-dose radiotherapy damages cell DNA causing previously hidden or difficult-to-recognize tumor antigens to be exposed on the cell surface This change promotes the cross-presentation of tumor-specific antigens increases lymphocyte infiltration into the tumor site enhances tumor-specific immune responses and further improves the efficacy of immune checkpoint inhibitors Preoperative immunotherapy can activate the patients immune system enabling it to recognize tumor antigens and establish immune memory This allows the immune system to continue to function in immune surveillance after the surgical removal of the tumor Currently the main focus of clinical research is on how to maximize the synergistic effects between different treatment modalities to achieve the best survival outcomes for patients with locally advanced esophageal cancer while minimizing treatment side effects
This study is a Phase IIA clinical trial a preliminary study of efficacy and safety This study envisions a comprehensive treatment of neoadjuvant low-dose radiotherapy combined with chemotherapy and immunotherapy chemo-immuno which by reducing the radiotherapy dose can enhance local control efficacy and reduce adverse reactions caused by the combined treatment mode Therefore it is proposed to perform neoadjuvant low-dose radiotherapy combined with chemo-immuno treatment in patients with locally advanced esophageal squamous cell carcinoma adjust the preoperative radiotherapy dose from 40 Gy20f to 4 Gy2f evaluate the efficacy and safety of this treatment mode and provide more evidence for the neoadjuvant treatment model for locally advanced esophageal cancer patients Additionally exploratory analyses of preoperative and postoperative tissue and blood samples will be conducted to understand the impact of preoperative low-dose radiotherapy combined with immunotherapy on the esophageal cancer immune microenvironment suitable biological markers will be selected to identify the optimal beneficiary group
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