Neoadjuvant Immunotherapy to ESCC

Phase 2

Withdrawn

• Conditions: Esophagus SCC
• Interventions: Drug: Paclitaxel and Cisplatin; Drug: Sintilimab Injection plus Paclitaxel and Cisplatin

• Registration Number: NCT04625543
• Lead Sponsor: Qilu Hospital of Shandong University

Brief Summary

Currently, surgery after neoadjuvant chemoradiotherapy is the standard treatment for patients with locally advanced esophageal cancer, but the recurrence rate is high and the 5-year survival rate is low. Immunotherapy shows a potential treatment for esophageal cancer. Immunocheckpoint (PD-1/PD-L1) inhibitors can activate tumor immunity. The guidelines have recommended it as a sencond-line therapy. However, there is still lack of the evidence for its efficacy as a neoadjuvant therapy. This study is to conduct a randomized controlled, open label, phase II clinical trial to evaluate the efficacy and safety of neoadjuvant immnotherapy combined with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) patient with PD-L1 (CPS\>=10%) positive.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-11-06
• Study First Submitted QC: 2020-11-06
• Study First Posted: 2020-11-12
• Study Start: 2020-12
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-19
• Last Update Posted: 2022-04-26
• Primary Completion: 2023-06
• Study Completion: 2023-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Volunteer to participated and sign information consent;
2. Age 18-70, male or female;
3. Locally advanced esophageal cancer diagnosed by pathology, Clinical tumor stage should be II-IVa; tumor located at the lower middle segment;
4. No previous chemoradiotherapy or immunotherapy;
5. PD-L1 expression >=10%;
6. Have a performance status of 0 or 1 on the ECOG Performance Scale;
7. Demonstrate adequate organ function as defined below (excluding the use of any blood components and cytokines during the screening period): Absolute neutrophil count (ANC) ≥1.5*109 /L; Platelet ≥100*109/L; Hemoglobin ≥ 9 g/dL; Serum albumin≥3g/dL; Bilirubin≤1.5 x ULN; ALT and AST≤2.5 ULN; Serum creatinine ≤1.5 x ULN or creatinine clearance ≥40mL/min; LVEF>=50%; Urine protein<++; INR<1.5 and APTT<1.5;
8. Female subject must have taken reliable contraceptive measures of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. and be willing to use an appropriate method of contraception during the trial and 8 weeks after the last administration of the test drug. Male subject should agree to use appropriate contraceptive methods or to have been surgically sterilized during the trial and 8 weeks after the last administration of the test drug.

Exclusion Criteria

1. Any active autoimmune disease or history of autoimmune disease (as follows, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitritis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction);
2. Asthma requiring medical intervention with bronchodilators was not included.
3. Subjects with history of severe allergy;
4. There are clinical symptoms or diseases of the heart that are not well controlled, such as: heart failure above grade 2 by the Criteria of NYHA; unstable angina pectoris; myocardial infarction occurred within 1 year; Clinically meaningful supraventricular or ventricular arrhythmias require treatment or intervention;
5. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), or has known active Hepatitis B (e.g. HBV DNA≥ 2000IU/ml or copy number ≥104/ml;) or Hepatitis C (e.g. HCV antibody positive);
6. Systematic glucocorticoid therapy is administered one week prior to neoadjuvant therapy;
7. Subjects who are participating other drug clinical trials.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
controll group	Paclitaxel and Cisplatin	Neoadjuvant chemotherapy (paclitaxel + Cisplatin) will be applied to patients with locally advanced esophageal squamous cell carcinoma with PD-L1\>=10% before surgery.
intervention group	Sintilimab Injection plus Paclitaxel and Cisplatin	Neoadjuvant immunotherapy (PD-1) plus concurrent chemotherapy (paclitaxel + Cisplatin) will be applied to patients with locally advanced esophageal squamous cell carcinoma with PD-L1\>=10% before surgery.

Primary Outcome Measures

Name	Time	Method
Major Pathological Response (MPR) rate	30 days after the second cycle of treatment(each cycle is 21 days)	MPR is defined as 10% or fewer viable cancer cells in the hematoxylin and eosin (H\&E)-stained slides from the resected tumor following neoadjuvant treatment.

Secondary Outcome Measures

Name	Time	Method
2-year progression-free survival (PFS)	every 3 months (up to 24 months)	From date of surgery until the date of first documented progression or date of death from any cause
Objective Response Rate (ORR)	at the end of the second cycle of treatment(each cycle is 21 days)	ORR determines the tumor shrinkage rate, tumor boundary and the adhesion of tumor
The incidence of adverse events	the day from the first treatment cycle	Safety will be evaluated for all treated patients using CTCAE V 5.0.

Trial Locations

Locations (1)

Qilu Hospital of Shandong University; 🇨🇳 Jinan, Shandong, China