Carrelizumab, Chemotherapy and Apatinib in the Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma

A Prospective, One-arm, Single-center, Phase Ⅱ Clinical Study of Carrelizumab Combined With Chemotherapy and Antiangiogenic Drugs in the Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma

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 Carrillizumab provided higher overall response rate for advanced esophageal cancer.

However, in patients with locally advanced esophageal cancer, the efficacy of Carrillizumab combined with chemotherapy and apatinib for sequential radical surgery is still unclear. The purpose of this study is to observe and evaluate the efficacy and safety of Carrillizumab combined with chemotherapy and antiangiogenic drugs in the neoadjuvant therapy of resectable esophageal squamous cell carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoadjuvant Therapy; Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Procedure: Esophagectomy; Drug: Carillizumab; Other: Samples

Detailed Description

Esophageal cancer is a common malignant tumor of the digestive tract. Every year, there are about 400,000 new cases of esophageal cancer in the world and about 300,000 people dying of this disease. 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. Early local invasion, lymph node metastasis and distant metastasis are the main causes of poor prognosis for the patients with esophageal squamous cell carcinoma.

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.

In recent years, PD-1 antibody is undoubtedly the most dazzling star in the field of tumor therapy. It shows excellent efficacy in of the different kind of tumors. According to the reports, the expression of PD-L1 in esophageal cancer was about 41.4% (Meta-analysis of 1350 Chinese and Japanese subjects showed that the over-expression of PD-L1 tended to decrease overall survival). 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 Carrillizumab provided higher overall response rate for advanced esophageal cancer. It also provided superior progression free survival and overall survival compared with Pembrolizuma and paclitaxel. 2020 Chinese Society Of Clinical Oncology esophagus cancer guidelines recommended Carrillizumab as the first level for squamous cell carcinomas.

However, in patients with locally advanced esophageal cancer, the efficacy of Carrillizumab combined with chemotherapy and apatinib for sequential radical surgery is still unclear. The purpose of this study is to observe and evaluate the efficacy and safety of Carrillizumab combined with chemotherapy and antiangiogenic drugs in the neoadjuvant therapy of resectable esophageal squamous cell carcinoma.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hangzhou, China, 310009
    • 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Carillizumab; Preoperative neoadjuvant therapy for 2-3 cycles. Radical surgery is performed 4-6 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient. Carillizumab can be maintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.

Procedure: Esophagectomy; Laparoscopy combined with thoracoscope radical resection of esophageal carcinoma; Drug: Carillizumab; administration regimen: Carillizumab 200mg, IV, D1; Albumin paclitaxel 150mg/m2, D1; Nedaplatin 50 mg/m2, D1; Apatinib 250mg Po D2-4. Preoperative neoadjuvant therapy for 2-3 cycles, one cycle every 14 days.; Other Names: Esophagectomy; Collecting samples from participant; Other: Samples; Blood, Tumour and Saliva will be Collected from participant. Fate of sample is Destruction after use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (PCR)	No residual invasive tumor cells were found in the pathological examination of resected specimens.	1 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Incidence of Treatment-related Adverse Events	Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0	1 month after surgery
Objective Response Rate (ORR)	The proportion of subjects with imaging PR or CR assessed according to RECIST 1.1 criteria	1 month after surgery
2-year and 5-year disease-free survival	No recurrence, distant metastasis, or death within 2 years and 5 years after surgery accounted for the proportion of all cases studied.	2-year and 5-year after surgery
R0 resection rate	The pathological results showed that the incision margin was negative and no residual cancer cells were found under the microscope	1 month after surgery
The changes in the peripheral blood immunoprofile among non-PCR (NPCR) and PCR patients	By using mass spectrometry (CyTOF) and bioinformatics pipelines, we comprehensively characterized the immune landscape in the peripheral blood of ESCC patients before and after anti-PD-1 immunotherapy, aiming to explore the immune subsets correlated with neoadjuvant immunotherapy response	3 month after surgery

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Weilin Wang, 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Estimated): November 1, 2030

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Apatinib; Esophageal Squamous Cell Carcinoma; Neoadjuvant Treatment; Carrelizumab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: 2020-795

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No