A Perioperative Sintilimab and Chemotherapy in Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This study is aimed to evaluate the efficacy and safety of sintilimab combined with chemotherapy versus chemotherapy in perioperative treatment of locally advanced esophageal squamous cell carcinoma.

Detailed Description
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This study was designed as an open-label, randomized controlled, phase II trial. Subjects will be systematically randomized at a ratio of 1:1 and will be assigned to either the experimental group (sintilimab combined with chemotherapy group) or the control group (chemotherapy alone group). They will receive 2-3 cycles of neoadjuvant therapy followed by radical esophagectomy and lymph node dissection and adjuvant therapy determined by investigators. The primary endpoint is 1-year Event-free survival (EFS) rate.

Official Title
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A Prospective, Open-label, Randomized, Phase II Study of the Efficacy and Safety of Sintilimab Combined With Chemotherapy Versus Chemotherapy in Perioperative Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma (ECTOP-2006).

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Sintilimab
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Esophageal squamous cell carcinoma suggested by gastroscopic histopathology. The primary tumor is located in the middle and lower of the esophagus. cT2-4aN0～3M0 or cT1N+M0 diagnosed by enhanced CT/MRI scan. Tumor was evaluated as resectable by surgeon before neoadjuvant therapy. Eastern cooperative oncology group (ECOG) performance status of 0 to 1. Can eat semi-liquid food. Less than 20% body weight loss within 6 months prior to enrollment. Sign the consent form before treatment and be able to comply with the relevant procedures such as treatment and visits stipulated in the protocol. With adequate organs function 1 week before enrollment and tolerable to chemotherapy and surgery. Female subjects of childbearing age or male subjects whose sexual partners are females of childbearing age should take effective contraceptive measures throughout the treatment period and 180 days after the last dose of the test drug. Agree and be able to provide archived or fresh pathological tissue and whole blood, urine and fecal samples for biomarker testing. Exclusion Criteria: With metastases or unresectable primary lesion suggested by imaging before treatment. History of previous subtotal gastrectomy. Patients with active malignancy within 2 years other than the tumor studied in this study or a localized tumor that has been cured such as resected basal or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or breast cancer. Received any anti-tumor therapy for the research disease in the past, including radiotherapy, chemotherapy, immunotherapy (including but not limited to interleukin, interferon, thymus hormone) and traditional Chinese medicine therapy. With signs of pre-esophageal perforation. With any active autoimmune disease or has a history of autoimmune disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sintilimab plus chemotherapy<br>Sintilimab: 200mg; cisplatin: 75mg/m2, d1, routine hydration for 3 days; nab-paclitaxel: 260mg/m2, d1, every 3 weeks, 2-3 cycles. | Drug: Sintilimab<br>* Sintilimab (200mg) will be given intravenously on day 1 in 3-week cycles for 2-3 cycles.<br>Drug: Chemotherapy<br>* Cisplatin (75mg/m2) wih routine hydration for 3 days and nab-paclitaxel (260mg/m2) will be given intravenously on day 1 in 3-week cycles for 2-3 cycles.<br>|
| Active Comparator: Chemotherapy<br>Cisplatin: 75mg/m2, d1, routine hydration for 3 days; nab-paclitaxel: 260mg/m2, d1, every 3 weeks, 2-3 cycles. | Drug: Chemotherapy<br>* Cisplatin (75mg/m2) wih routine hydration for 3 days and nab-paclitaxel (260mg/m2) will be given intravenously on day 1 in 3-week cycles for 2-3 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival (EFS) | EFS is defined as the time from R0 resection to disease recurrence or metastases or death for subjects achieving radical resection or the time from enrollment to disease progression or death for subjects not achieving radical resection. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 surgery rate | R0 resection is defined as no cancer cells are seen microscopically at the resection margin following surgery. | 20 months | 
| pCR rate | Pathological Complete Response (pCR) is defined as no viable cancer cells in the hematoxylin and eosin (H&E)-stained slides from the resected tumor and lymph nodes following neoadjuvant treatment. | 20 months | 
| Disease-free survival (DFS) | DFS is calculated from R0 surgery to the date of recurrence or metastases or death in subjects with radical resection. | 24 months | 
| Overall Survival (OS) | OS is calculated from the randomization to the date of death from any cause. | 24 months | 
| adverse events | The incidence of treatment-related adverse events (TRAEs), severe adverse events (SAE), based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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perioperative, esophageal cancer, programmed cell death protein-1 inhibitor