Esophageal Squamous Cell Carcinoma, Neoadjuvant Treatment
Conditions
Keywords
Adbelimumab, Chemotherapy, Apatinib, Esophageal Squamous Cell Carcinoma, Neoadjuvant Treatment
Brief summary
Esophageal cancer is a prevalent digestive tract tumor, with around 400,000 new cases and 300,000 deaths globally each year. In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma (ESCC) 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 ESCC. Preliminary clinical results showed that immunotherapy combined with chemoradiotherapy provided a synergies antitumor effect. The results of the Phase 1b trial evaluating adbelimumab monotherapy as a neoadjuvant treatment for locally advanced resectable ESCC demonstrated that patients receiving two cycles of neoadjuvant sequential surgery exhibited favorable safety profiles, with no adverse reactions of grade 3 or higher. The trial reported a major pathological response (MPR) rate of 24%, a pathological complete response (pCR) rate of 8%, a 2-year overall survival (OS) rate of 92%, and a 2-year recurrence-free survival (RFS) rate of 100%. The effectiveness of combining adbelizumab with chemotherapy and targeted therapy for locally advanced esophageal cancer is uncertain. This study aims to assess the efficacy and safety of using adbelizumab with chemotherapy and apatinib as neoadjuvant therapy for resectable ESCC.
Interventions
DRUGAdbelimumab, Albumin paclitaxel, Carboplatin, Apatinib
Adbelimumab 1200mg Day 1; Albumin paclitaxel 260mg/m2, Day 1; carboplatin AUC=5, Day 1; Apatinib 250mg Po Day 2-4. Preoperative neoadjuvant therapy for 4 cycles, one cycle every 21 days.
PROCEDUREEsophagectomy
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 IvorLewis (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.
OTHERCollecting samples from participant
Blood, Tumour will be Collected from participant. Fate of sample is Destruction after use. 20 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.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 II-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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (PCR) | 1 month after surgery | The pCR will be defined as the proportion of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | before surgery | The ORR will be defined as the proportion of participants who have a complete response or partial response before surgery as assessed by the investigator per RECIST v1.1 in all participants with measurable disease at baseline |
| The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients | 3 months after surgery | 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. |
| Major Pathological Response (MPR) | 1 month after surgery | The MPR will be defined as the proportion of participants with less 10% of residual tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant treatment. |
| Incidence of Treatment-related Adverse Events | 1 month after surgery | Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0 |
| R0 resection rate | 1 month after surgery | This will be defined as the proportion of participants with R0 resection |
| 2-year and 5-year overall survival | 2-year and 5-year after enrolled | The proportion of all study cases in which no death from any cause occurred within 2 years and 5 years after enrolled |
Countries
China
Contacts
Primary ContactMing Wu, M.D
Outcome results
None listed