Serplulimab Combined With Chemotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

A Prospective, Single-arm, Single-center, Exploratory Study of the Safety and Efficacy of Serplulimab Combined With Chemotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05659251
• Other study ID #: 2022-1022
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2022
• Est. completion date: December 31, 2029

Study information

• Verified date: November 2023
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Ming Wu, M.D
• Phone: +8613757118715
• Email: iwuming22[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

China with high incidence of esophageal cancer, the number of new cases and deaths account for about 50% of the world every year. In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma patients was not significantly decreased. For patients with locally advanced esophageal cancer, direct surgery is not effective. It is difficult to achieve radical resection by surgery merely, and even if many patients receive surgery, they may eventually have tumor recurrence and poor survival rate. Therefore, it is necessary to explore effective perioperative neoadjuvant treatment to reduce the risk of postoperative recurrence and improve the postoperative survival rate of patients. According to the reports, the expression of PD-L1 in esophageal cancer was about 41.4%. Therefore, PD-1/ PD-L1 immunocheckpoint inhibitor may become a new method for the treatment of esophageal cancer. Preliminary clinical results showed that immunotherapy combined with chemoradiotherapy provided a synergies antitumor effect. Multiple clinical results showed that serplulimab provided higher overall response rate for advanced esophageal cancer. However, in patients with locally advanced esophageal cancer, the efficacy of serplulimab combined with chemotherapy for sequential radical surgery is still unclear. The purpose of this study is to observe and evaluate the efficacy and safety of silulimab combined with chemotherapy in the neoadjuvant therapy of resectable esophageal squamous cell carcinoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 49
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. signed informed consent;

2. patients age 18 to 75 years old

3. primary resectable, histologically confirmed esophageal squamous cell cancer;

4. Esophageal squamous cell carcinoma the clinical stage was IIA-IVA (according to AJCC TNM stage, 8th edition).

5. ECOG PS 0-1.

6. No distant metastasis, the diseases could be resectable assessed by thoracic oncologist;

Exclusion Criteria:

1. with significant cardiovascular disease;

2. current treatment with anti-viral therapy or HBV;

3. Female patients who are pregnant or lactating;

4. history of malignancy within 5 years prior to screening;

5. active or history of autoimmune disease or immune deficiency;

6. signs of distant metastases.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Neoadjuvant Therapy

Intervention

Combination Product:
• Serplulimab, Albumin paclitaxel, carboplatin AUC=5, neoadjuvant therapy
Serplulimab 4.5mg/kg, IV, Day 1; Albumin paclitaxel 260mg/m2, Day 1; carboplatin AUC=5, Day 1; Preoperative neoadjuvant therapy for 2-4 cycles, one cycle every 21 days.

Procedure:
• Esophagectomy
Prior to each surgical procedure, the department engaged in comprehensive discussions and deliberations to ascertain and establish the most suitable course of action. Minimally invasive Ivor-Lewis (intrathoracic anastomosis) or McKeown (neck anastomosis) esophagectomy, including two field extensive lymphadenectomies, was performed according to the tumor location. The resection length should be at least 5cm from the tumor origin according to prechemotherapy by endoscopy. The surgeries will be performed by surgeons with rich experience. Minimally invasive esophagectomy, can be performed using the da Vinci surgical robot, thoracoscope, or laparoscope, or by using an open approach, as judged appropriate by the surgeon.

Other:
• sample
Blood, Tumour will be Collected from participant. Fate of sample is Destruction after use. 5 ml of peripheral blood was collected the day before each of the immunotherapy sessions and after surgery. Tumour sample will be collected before neoadjuvant therapy and after surgery.

Locations

Country	Name	City	State
China	2nd Affiliated Hospital, School of Medicine, Zhejiang University	Hangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological Complete Response (PCR)	No residual invasive tumor cells were found in the pathological examination of resected specimens, including the primary tumor and lymph nodes.	1 month after surgery
Secondary	major pathological response (MPR)	In the pathological examination of resected specimens, the proportion of residual tumor cells was less than 10%.	1 month after surgery
Secondary	Objective Response Rate (ORR)	The proportion of subjects with imaging PR or CR assessed according to RECIST 1.1 criteria	before surgery
Secondary	2-year and 5-year overall survival	The proportion of all study cases in which no death from any cause occurred within 2 years and 5 years after surgery	2-year and 5-year after surgery
Secondary	Incidence of Treatment-related Adverse Events	Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0	1 month after surgery
Secondary	R0 resection rate	The pathological results will showed that the incision margin was negative and no residual cancer cells were found under the microscope	1 month after surgery
Secondary	The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients	By using mass spectrometry (CyTOF) and single-cell analysis, we comprehensively characterized the immune landscape in the peripheral blood and tumor sample of ESCC patients before and after anti-PD-1 immunotherapy, aiming to explore the immune subsets correlated with neoadjuvant immunotherapy response.	3 months after surgery