Neoadjuvant Immunotherapy to ESCC

NCT ID: NCT04625543

Last Updated: 2022-04-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-31
• Study Completion Date: 2023-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sintilimab Injection plus Paclitaxel and Cisplatin

Intervention Type: 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.

controll group

Neoadjuvant chemotherapy (paclitaxel + Cisplatin) will be applied to patients with locally advanced esophageal squamous cell carcinoma with PD-L1\>=10% before surgery.

Group Type: ACTIVE_COMPARATOR

Paclitaxel and Cisplatin

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Qilu Hospital of Shandong University

OTHER

Sponsor Role: lead

Responsible Party

Sang Shaowei

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shaowei Sang, Doctor

Role: PRINCIPAL_INVESTIGATOR

Qilu Hospital of Shandong University

Locations

Qilu Hospital of Shandong University

Jinan, Shandong, China

Countries

China

Other Identifiers

NEO-PD-1-II-ESCC

Identifier Type: -

Identifier Source: org_study_id