Neoadjuvant Immunotherapy to ESCC

Neoadjuvant Immunotherapy Combined With Neoadjuvant Chemotherapy for Locally Advanced Esophageal Cancer: an Open Label, Randomized Control, Phase II Trial

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.

Study Overview

• Status: Withdrawn
• Conditions: Esophagus SCC
• Intervention / Treatment: Drug: Sintilimab Injection plus Paclitaxel and Cisplatin; Drug: Paclitaxel and Cisplatin

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: intervention group; 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.	Drug: Sintilimab Injection plus Paclitaxel and Cisplatin; Paclitaxel 150mg/m2 on day 1, every 3 weeks, for two cycles; Cisplatin 70mg/m2 on day 1, every 3 weeks, for two cycles; Sintilimab Injection 200mg on day 22; 4-6 weeks after completion of preoperative therapy, Mckeown esophagectomy will be performed if there is no contraindication.
Active Comparator: controll group; Neoadjuvant chemotherapy (paclitaxel + Cisplatin) will be applied to patients with locally advanced esophageal squamous cell carcinoma with PD-L1>=10% before surgery.	Drug: Paclitaxel and Cisplatin; Paclitaxel 150mg/m2 on day 1, every 3 weeks, for two cycles; Cisplatin 70mg/m2 on day 1, every 3 weeks, for two cycles; 4-6 weeks after completion of preoperative therapy, Mckeown esophagectomy will be performed if there is no contraindication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) rate	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.	30 days after the second cycle of treatment(each cycle is 21 days)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Principal Investigator: Shaowei Sang, Doctor, Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: neoadjuvant; ESCC; Randomized controlled clinical trial; PD-1/PD-L1
• 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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NEO-PD-1-II-ESCC

Drug and device information, study documents

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