A Perioperative Sintilimab and Chemotherapy in Esophageal Squamous Cell Carcinoma

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).

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Sintilimab; Drug: Chemotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 182
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haiquan Chen, MD; Phone Number: +86 13601973588; Email: hqchen1@yahoo.com
• Study Contact Backup: Name: Bin Li, MD; Phone Number: +86 18017317295; Email: lb0256327@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Haiquan Chen, MD; Phone Number: +86 13601973588; Email: hqchen1@yahoo.com
      • Principal Investigator: Haiquan Chen, MD
      • Sub-Investigator: Bin Li, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Innovent Biologics (Suzhou) Co. Ltd.
• Investigators: Principal Investigator: Haiquan Chen, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): December 15, 2023
• Primary Completion (Estimated): December 15, 2025
• Study Completion (Estimated): December 15, 2027

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: esophageal cancer; perioperative; programmed cell death protein-1 inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: ECTOP-2006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No