A Phase Ⅱ Trials of Sintilimab as Consolidation Therapy After Radical Concurrent Chemoradiotherapy in Locally Advanced Unresectable ESCC

The purpose of this study is to observe and evaluate the efficacy and safety of Sintilimab for Consolidation Therapy After Radical Concurrent Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Cisplatin+Capecitabine+Sintilimab

Detailed Description

In China, the incidence of esophageal cancer has declined in recent years, but the mortality rate has been ranked fourth. Morbidity and mortality were ranked sixth and fourth in all malignancies, respectively. Therefore, esophageal cancer has always been a major malignant tumor that threatens the health of our residents.We designed a single-arm, open-label, phase II trial of Sintilimab for consolidation therapy after radical concurrent chemoradiotherapylocally advanced esophageal squamous cell carcinoma.The purpose of this study is to observe and evaluate the efficacy and safety of Sintilimab for consolidation therapy after radical concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhengzhou, China, 450001
    • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-75 years old, both men and women; 2. Histology confirmed as esophageal squamous cell carcinoma; 3. T1bN+M0, T2-T4aN0-2M0 locally advanced stage； 4. Tissue samples should be provided for biomarker analysis, and the newly obtained tissues should be selected. Patients who cannot provide newly obtained tissues can provide 5-8. pieces of 5-um thick paraffin sections; 5. ECOG: 0~1; 6. Expected survival period ≥ 12 weeks; 7. The main organs function normally, that is, the following criteria are met:

1. Blood routine examination:

   1. HB≥90g/L;
   2. ANC ≥ 1.5 × 109 / L;
   3. PLT ≥ 80 × 109 / L;

2. Biochemical examination:

   1. ALB ≥ 30g / L;b.ALT and AST ≤ 2.5ULN; if there is liver metastasis, ALT and AST ≤ 5ULN;c.TBIL ≤ 1.5ULN;d.plasma Cr ≤ 1.5ULN or creatinine clearance (CCr) ≥ 60ml / min; 8.Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%); 9. Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; negative serum or urine pregnancy test within 7 days prior to study enrollment And must be non-lactating patients; males should agree to patients who must use contraception during the study period and within 6 months after the end of the study period; 10. Subjects voluntarily joined the study, signed informed consent, and were well-adhered to follow-up.

Exclusion Criteria:

1. Does not meet the above inclusion criteria;
2. Those who are allergic to or sensitive to capecitabine and cisplatin or metabolic disorders;
3. The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis,Hyperthyroidism; patients with vitiligo ; Asthma has been completely relieved in childhood, and patients who do not need any intervention after adulthood can be included; asthma patients who require bronchodilators for medical intervention cannot be included);
4. The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppressive purposes (dose> 10 mg/day of prednisone or other therapeutic hormones) and continues to be used for 2 weeks prior to enrollment;
5. contraindications to radiotherapy;
6. Patients with any severe and/or uncontrolled diseases:Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100 mmHg); myocardial ischemia or myocardial infarction with grade I or above, arrhythmia (including QT interval ≥ 480ms) and grade I cardiac insufficiency;
7. Active or uncontrolled serious infections;
8. Liver diseases such as decompensated liver disease, active hepatitis B (HBV-DNA ≥ 104 copies/ml or 2000 IU/ml) or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the lower limit of detection of the analytical method);
9. Urine routine indicates that urine protein ≥ ++, and confirmed 24-hour urine protein quantitation> 1.0g;
10. The patients whose imaging showed that the tumor had invaded the important vessels or the tumor was likely to invade the important vessels and cause fatal hemorrhage during the follow-up study;
11. Pregnant or lactating women;
12. Patients with other malignancies within 5 years (except for basal cell carcinoma and cervical carcinoma in situ) that have been cured;
13. Patients with a history of psychotropic substance abuse who are unable to quit or have a mental disorder;
14. Patients who have participated in other drug clinical trials within four weeks;
15. At the discretion of the investigator, there are patients with serious concomitant disease that compromises patient safety or affects the patient's completion of the study;
16. The investigator believes that it is not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cisplatin+Capecitabine+Sintilimab	Drug: Cisplatin+Capecitabine+Sintilimab; The first stage:concurrent chemoradiotherapy，cisplatin，25-30mg/m2 ivgtt d1;capecitabine,800mg/m2, bid d1-5，qw，5weeks;concurrent radiotherapy,1.8-2Gy/d，5d/W，50-50.4Gy. second stage:Sintilimab, 200mg,q3w, a total of 3 times，Each infusion lasted for 30-60 min until disease progression or intolerable toxicity, with a maximum duration of no more than 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival（PFS）	Evaluation of anti-PD-1 antibody Sintilimab for progression-free survival in patients with locally advanced unresectable esophageal squamous cell carcinoma who did not develop disease after radical concurrent chemoradiotherapy	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate，ORR	To evaluate the objective response rate (objective response rate, ORR) of Sintilimab in patients with locally advanced esophageal squamous cell carcinoma who have not progressed after concurrent radiotherapy and chemotherapy	At time of surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analysis of biomarkers for predicting efficacy	The relationship between PD-L1 dynamic expression, ctDNA sequencing and therapeutic effect was evaluated	At time of surgery
Overall survival, OS	From date of randomization until the date of death from any cause	At time of surgery

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2021
• Primary Completion (Anticipated): January 31, 2022
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 19, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: IBI308-01

Drug and device information, study documents

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