Oesophageal Squamous Cell Carcinoma
Conditions
Brief summary
The investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable esophageal squamous cell carcinoma (ESCC).
Detailed description
Host immunity is critical to the development and progression of tumor. PD-1 is the co-inhibitory receptor in many immunity cells while PD-L1, the ligands for PD-1, is expressed in tumor cell and is associated with prognosis. Previous studies have shown that anti-PD-1/PD-L1 antibody had durable responses in patients with advanced malignant tumors such as melanoma, renal cell cancer, lung cancer and esophagus cancer. SHR-1316 (Hengrui Medicine, China), anti-PD-L1 antibody, could induce the elevated secretion of interferon (IFN)-α and showed significant tumor-suppression effect in vivo. The phase III clinical trial on the SHR-1316 versus placebo combines with carboplatin and etoposide in the patients with small cell lung cancer is currently being studied (SHR-1316-III-301). Esophagus cancer usually has a poor prognosis and esophagus squamous cell carcinoma (ESCC) is the main histological type in China. Combination with operation and neoadjuvant therapy including radiotherapy or/and chemotherapy is considered the standard therapy for local advanced esophagus cancer. However, no studies focused on the neoadjuvant immunotherapy in resectable esophagus have been reported. Therefore, the investigators will conduct a prospective, single-arm study to evaluate the safety and feasibility of neoadjuvant therapy with anti-PD-L1 antibody (SHR-1316, Hengrui Medicine) in patients with resectable ESCC. The primary objectives included the tumor regression grade, adverse event, safety of operation, complications and 30-day mortality. Our study will also explore the relation of tumor immune milieu, circulating immune cells, soluble factors, circulating tumor cell in the patients. Data from our study will provide the basis for further prospective clinical trials (Phase III). Finally, the investigators aim to discover the biomarkers of response and toxicity to allow patients with ESCC derive more benefit from immunotherapy and minimize the risk of toxicity.
Interventions
DRUGPD-L1 Antibody SHR-1316
Neoadjuvant therapy with immunoreagent (PD-L1 antibody SHR-1316) for resectable oesophageal squamous cell carcinoma
Sponsors
Shanghai Zhongshan Hospital
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
* The patients should be diagnosed with squamous cell cancer by gastroscopic biopsies and the tissue samples should be collected before the treatment. * The primary tumor should be located in the thorax; the primary site is decided by the upper margin of the mass (upper thoracic esophagus: from the thoracic inlet to inferior margin of azygos arch, the endoscopic examination shows 20-25cm to the incisor; middle thoracic esophagus: from inferior margin of azygos arch to the inferior pulmonary vein level, the endoscopic examination shows 25-30cm to the incisor; lower thoracic esophagus: from the inferior pulmonary vein level to the stomach, the endoscopic examination shows 30-40cm to the incisor). * The patients should be evaluated to be able to have surgical resection before the surgery according to the examinations (use enhanced thoracic and abdominal CT, cervical lymph node ultrasound to evaluate whether the tumor has obvious invasion, whether there are enlarged mediastinal lymph nodes; use examinations including positron emission computed tomography (PET-CT), endoscopic ultrasonography (EUS) to make further clinical staging if considering the primary tumor as T4b, multiple mediastinal lymph nodes metastasis or distant metastasis). * The patients should be at the range of 18-75 years old, Eastern Cooperative Oncology Group (ECOG) 0-1, the estimated survival time should be over 12 months. * The recipients should have no functional disorders in main organs. Blood routines, functions of lung, liver, kidney and heart should be basically normal, the label test index should accord with the demands as follows: Blood: white blood cell count (WBC)\>4.0\*10\^9/L, absolute neutrophil count (ANC)≥2.0\*10\^9/L, platelet count (PLT)\>100\*10\^9/L, hemoglobin (HBG)\>90g/L; Pulmonary function: Forced Expiratory Volume in the first second (FEV1)≥1.2 L, FEV1%≥50%, carbon monoxide diffusing capacity (DLCO)≥50%; Liver function: Serum bilirubin should be lower than 1.5 times of the maximum normal value; Alanine aminotransferase (ALT) and Aspartate transaminase (AST) should be lower than 1.5 times of the maximum normal value; Renal function: serum creatinine (SCr)≤120μmol/L creatinine clearance rate （CCr）≥60ml/min; * The patients should be able to understand our research and sign the informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response | Through the study completion, an average of 12 weeks | The primary endpoint is objective response (according to the Response Evaluation Criteria In Solid Tumors, version 1.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events and treatment-related adverse events | Through the study completion, an average of 12 weeks | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
| Correlation between genetic profile and tumor response | Through the study completion, an average of 12 weeks | Genetic profile (assessed by whole exome sequencing, T-cell receptor sequencing, RNA sequencing) will be correlated with tumor objective response |
Countries
China
Contacts
Primary ContactLijie Tan, MD, PhD
Backup ContactJun Yin, MD, PhD
Outcome results
None listed