Neoadjuvant Immunotherapy to ESCC

NCT04625543 | Withdrawn Phase 2

• 1 other identifier: NEO-PD-1-II-ESCC
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophagus SCC

Keywords

ESCC; PD-1/PD-L1; Randomized controlled clinical trial; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Objective Response Rate (ORR)

  at the end of the second cycle of treatment(each cycle is 21 days)

• 2-year progression-free survival (PFS)

  every 3 months (up to 24 months)

• The incidence of adverse events

  the day from the first treatment cycle

Study Arms (2)

intervention group

EXPERIMENTAL

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

controll group

ACTIVE COMPARATOR

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

Interventions

Sintilimab Injection plus Paclitaxel and Cisplatin DRUG

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.

intervention group

Paclitaxel and Cisplatin DRUG

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.

controll group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteer to participated and sign information consent;
• Age 18-70, male or female;
• Locally advanced esophageal cancer diagnosed by pathology, Clinical tumor stage should be II-IVa; tumor located at the lower middle segment;
• No previous chemoradiotherapy or immunotherapy;
• PD-L1 expression \>=10%;
• Have a performance status of 0 or 1 on the ECOG Performance Scale;
• 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;
• 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.

You may not qualify if:

• 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);
• Asthma requiring medical intervention with bronchodilators was not included.
• Subjects with history of severe allergy;
• 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;
• 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);
• Systematic glucocorticoid therapy is administered one week prior to neoadjuvant therapy;
• Subjects who are participating other drug clinical trials.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

sintilimab; Paclitaxel; Cisplatin; TP protocol

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Shaowei Sang, Doctor

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 12, 2020
• Study Start: December 1, 2020
• Primary Completion: June 1, 2023
• Study Completion: September 1, 2023
• Last Updated: April 26, 2022

Record last verified: 2022-04

Locations

CN (1)