Neoadjuvant Immunotherapy to ESCC

• ClinicalTrials.gov Identifier: NCT04625543
• Recruitment Status: Not yet recruiting
• First Posted: November 12, 2020
• Last Update Posted: November 12, 2020
• Sponsor: Qilu Hospital of Shandong University
• Information provided by (Responsible Party): Sang Shaowei, Qilu Hospital of Shandong University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Esophagus SCC	Drug: Sintilimab Injection plus Paclitaxel and Cisplatin; Drug: Paclitaxel and Cisplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant Immunotherapy Combined With Neoadjuvant Chemotherapy for Locally Advanced Esophageal Cancer: an Open Label, Randomized Control, Phase II Trial
• Estimated Study Start Date: December 2020
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Major Pathological Response (MPR) rate [ Time Frame: 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 :

1. Objective Response Rate (ORR) [ Time Frame: 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
2. 2-year progression-free survival (PFS) [ Time Frame: 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
3. The incidence of adverse events [ Time Frame: the day from the first treatment cycle ]
   Safety will be evaluated for all treated patients using CTCAE V 5.0.

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Shaowei Sang, Doctor; +86 18560088260; sangshaowei@sdu.edu.cn

Locations

China, Shandong

Qilu Hospital of Shandong University

Jinan, Shandong, China, 250012

Contact: Hui Chen, Master +86 18560089579 huihui_chen1010@126.com

Sponsors and Collaborators

Qilu Hospital of Shandong University

Investigators

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

More Information

• Responsible Party: Sang Shaowei, Associate Professor, Qilu Hospital of Shandong University
• ClinicalTrials.gov Identifier: NCT04625543
• Other Study ID Numbers: NEO-PD-1-II-ESCC
• First Posted: November 12, 2020
• Last Update Posted: November 12, 2020
• Last Verified: November 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sang Shaowei, Qilu Hospital of Shandong University:

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

Additional relevant MeSH terms:

Esophageal Squamous Cell Carcinoma; 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; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action