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

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04666090
• Other study ID #: 2020-795
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 23, 2020
• Est. completion date: November 2030

Study information

• Verified date: November 2023
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: n/a
• 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 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: November 2030
• Est. primary completion date: December 31, 2022
• 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

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.

Procedure:
• Esophagectomy
Laparoscopy combined with thoracoscope radical resection of esophageal carcinoma

Other:
• Samples
Blood, Tumour and Saliva will be Collected from participant. Fate of sample is Destruction after use

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.	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	1 month after 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	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
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 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 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