Sintilimab in Combination With Chemotherapy in Neoadjuvant Treatment of Potentially Resectable Esophageal Cancer

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

Safety and Efficacy of Combination of Sintilimab and Platinum-based Chemotherapy in Neoadjuvant Treatment of Potentially Resectable Esophageal Cancer: An Open-lable, Single-arm, Exploratory Clinical Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03946969
• Other study ID #: KEEP-G 03
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 9, 2019
• Est. completion date: October 31, 2022

Study information

• Verified date: July 2022
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to investigate the safety and efficacy of sintilimab combined with platinum-based chemotherapy in neoadjuvant treatment of potentially resectable esophageal cancer.

Description:

This study was designed as an open-lable, single-arm, exploratory clinical study. Sintilimab in combination with liposomal paclitaxel, cisplatin and S-1 will be given every 3 weeks to our patients for 2 cycles as neoadjuvant therapy. A radical dissection is scheduled within 6 weeks after last neoadjuvant treatment. This study will be devided for 3 phases: safety run-in, efficacy pilot and efficacy confirmation.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: October 31, 2022
• Est. primary completion date: November 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Histologically or cytologically confirmed esophageal squamous cell carcinoma.

The tumor is located in the middle or lower third of the esophagus ( more than 18cm below incisor), potentially resectable and requiring neoadjuvant therapy (T1b-3, Nany, M0 or T4a, N0-1, M0).

No prior treatment for this disease.

Eastern cooperative oncology group (ECOG) performance status of 0 to 1.

Adequate bone marrow, liver, cardiac and renal function as assessed by the laboratory required by protocol.

Understand and voluntarily sign the informed consent(s).

Patients who are able to complete the treatment and follow-up according to the study plan.

Patients who have sufficient tissue samples and agree to provide their tissue samples and blood samples for detailed analysis.

Female patients in child bearing period must have evidence of negative pregnancy test and agree to take effective contraceptive measures during the study.

Exclusion Criteria:

Patients who may develop tracheoesophageal fistula or aortoesophageal fistula.

Patients suffering from severe malnutrition or needing tube feeding.

Uncured patients with other malignancies within 2 years.

Patients who have active autoimmune diseases or patients who are undergoing treatment of autoimmune diseases.

Patients who need systemic glucocorticosteroid treatment (more than 10mg prednisone daily or other equivalent drugs) within 7 days before the neoadjuvant therapy or other immunosuppressive drugs.

Patients who have immune deficiency.

Patients with active viral or bacterial infection who need systemic treatment within 7 days before the neoadjuvant therapy.

Patients with uncontrolled diabetes mellitus.

Patients with interstitial pulmonary disease, noninfectious pneumonia, or pulmonary fibrosis.

Patients with preexisting symptoms of sensory or motor nerve damage (greater than Grade 1, WHO) .

Patients who have received allogeneic organ or stem cell transplants.

Patients who are allergic to drugs or related ingredients in this study.

Patients who take part in clinical trials of other drugs or biological therapy at present.

Patients with any serious or unstable medical condition or mental illness.

Patients who are dependent on or addicted to alcohol or drugs.

Related Conditions & MeSH terms

• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• Sintilimab
Sintilimab (200mg) will be given intravenously on day 1 in 3-week cycles for two cycles.
• Liposomal Paclitaxel + Cisplatin + S-1
Liposomal Paclitaxel (135mg/m2), ivd, d1 + Cisplatin (25mg/m2), ivd, d1-3 + S-1 capsule (40mg), po, d1-14, repeated every 3 weeks for two cycles.

Locations

Country	Name	City	State
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University	Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Outcomes	Correlation between biomarkers, including tumor mutational burden (TMB), clonal mutations, genetic alterations, and circulating tumor DNA (ctDNA), and therapeutic response to neoadjuvant therapy will be explored.	20 months
Primary	Safety and feasibility	Safety is defined as the incidence of Grade 3-4 Treatment-Related Adverse Events (TRAEs) from the day of neoadjuvant therapy to 30 days after surgery or within 90 days after last neoadjuvant treatment. Feasibility of surgery is defined as the incidence of TRAEs causing surgery delay of =30 days and/or inoperable patients.	20 months
Secondary	MPR rate	Major Pathological Response (MPR) is defined as the presence of 10% or fewer viable cancer cells in the hematoxylin and eosin (H&E)-stained slides from the resected tumor following neoadjuvant treatment.	20 months
Secondary	R0 resection rate	R0 resection is defined as no cancer cells are seen microscopically at the resection margin following surgery.	20 months
Secondary	Recurrence-Free Survival (RFS)	Recurrence-Free Survival (RFS) is calculated from surgery to the date of recurrence or death.	5 years
Secondary	Overall Survival (OS)	Overall Survival (OS) is calculated from the beginning of neoadjuvant treatment to the date of death from any cause.	5 years