Clinical trial NCT04666090: Carrelizumab, Chemotherapy and Apatinib in the Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Neoadjuvant Therapy
Keywords: Carrelizumab
Neoadjuvant Treatment
Esophageal Squamous Cell Carcinoma
Apatinib
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2020-12-14
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathological Complete Response (PCR)
timeFrame: 1 month after surgery
Secondary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: 1 month after surgery
measure: Objective Response Rate (ORR)
timeFrame: 1 month after surgery
measure: 2-year and 5-year overall survival
timeFrame: 2-year and 5-year after surgery
measure: 2-year and 5-year disease-free survival
timeFrame: 2-year and 5-year after surgery
measure: Incidence of Treatment-related Adverse Events
timeFrame: 1 month after surgery
measure: R0 resection rate
timeFrame: 1 month after surgery
measure: The changes in the peripheral blood immunoprofile among non-PCR (NPCR) and PCR patients
timeFrame: 3 month after surgery
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
name: Weilin Wang
role: STUDY_CHAIR
References: