Neoadjuvant Immunotherapy to ESCC

Shandong University

Status and phase: Withdrawn; Phase 2

Conditions: Esophagus SCC

Treatments: Drug: Paclitaxel and Cisplatin; Drug: Sintilimab Injection plus Paclitaxel and Cisplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT04625543

NEO-PD-1-II-ESCC

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

intervention group

Experimental group

Description:

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.

Treatment:

Drug: Sintilimab Injection plus Paclitaxel and Cisplatin

controll group

Active Comparator group

Description:

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

Treatment:

Drug: Paclitaxel and Cisplatin