Selected Chemotherapy Combined Immunotherapy Treated High Risk Patient After NCRT in Resected Locally Advanced ESCC (ETNT)

University of Electronic Science and Technology of China (UESTC)

Status and phase: Active, not recruiting; Phase 2

Conditions: Esophageal Squamous Cell Carcinoma

Treatments: Drug: Tirelizumab; Radiation: Neoadiuvant radiotherapy; Drug: Carboplatin; Drug: Paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT05189730

SCCH-TS2107

Details and patient eligibility

About

Tislelizumab combined with chemotherapy sequential neoadjuvant therapy for non-cCR patients after neoadjuvant chemoradiotherapy in locally advanced ESCC. And then the patients would receive surgery and adjuvant therapy according to the postoperative pathological results. It is expected that through this study, some high-risk patients could obtain better efficacy and prolong patient survival. At same time, low risk patients could avoid increasing perioperative complications and surgical risks, so that more patients could benefit from neoadjuvant treatment. The investigators aimed to explore a more accurate comprehensive treatment mode for patients with esophageal squamous cell carcinoma, and provide a certain scientific basis for the formulation of esophageal cancer diagnosis and treatment norms in China.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1.Histologically confirmed ESCC；
• 2.Clinical stage T2N0-1M0, T3N0M0, T3N1M0, T1-3N2M0（II-III) (AJCC 8 TNM classif tion);
• 3.Locally advanced ESCC that can be treated surgically evaluated before treatment;
• 4.At least one measurable lesion in accordance with RECIST 1.1;
• 5.Have a performance status of 0 or 1 on the ECOG Performance Scale;
• 6.Expected survival time is greater than 6 months;
• 7.The important organs functions meet the following requirements:the absolute neutrophil count(ANC) ≥1.5×109/L; the platelet count ≥100×109/L; hemoglobin ≥90g/L; bilirubin is less than or equal to 1.5 times ULN, ALT and AST less than or equal 2.5 times UILN; creatinine clearance rate(CCr) ≥50mL/min; the thyroid function is normal;
• 8.Female subjects of childbearing potential have a negative pregnancy test and must agree to take effective contraceptive measures during the study period and within 3 months after the last dose;
• 9.Be willing and able to provide written informed consent/assent for the trial.

Exclusion criteria

• 1.The patient have received radiotherapy, chemotherapy, hormone therapy, surgery, or molecular-targeted therapy;
• 2.Confirmed patients with distant metastasis by CT imaging;
• 3.The subject has previous or co-existing other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
• 4.The subject had previously received other anti-pd-1 antibody therapy or other immunotherapy targeting pd-1 / pd-L1;
• 5.Patients with active autoimmune disease or documented autoimmune disease or symptoms requiring systemic hormone therapy or anti-autoimmune drug therapy;
• 6.Patients with immunodeficiency or who were still receiving systemic steroid hormone therapy (prednisone > 10 mg/ day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days prior to the first dose of neoadjuvant therapy in this study;
• 7.Clinical ascites or pleural effusion requiring therapeutic puncture or drainage;
• 8.The subject with uncontrol cardiac clinical symptoms or diseases, such as :(1) nyha class 2 or more heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant ventricular or ventricular arrhythmias requiring treatment or intervention;
• 9.Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg> 2G /L), bleeding tendency or receiving thrombolytic or anticoagulant treatment;
• 10.The subject is present (within 3 months) with esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension and other gastrointestinal diseases, or with active bleeding from unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator;
• 11.Past or present severe bleeding (bleeding >30 ml within 3 months), hemoptysis (fresh blood >5 ml within 4 weeks) or thromboembolism events (including stroke events and/or TRANSIENT ischemic attack) within 12 months;
• 12.Patients with active infection who still required systemic treatment 7 days before the first dose of neoadjuvant therapy in this study;
• 13.Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severely impaired lung function, etc;
• 14.Senior or uncontrolled virus injection: HIV, TP, hepatitis virus;
• 15.Senior or uncontrolled virus injection: HIV, TP, hepatitis virus;
• 16.Patients who had participated in clinical trials of other drugs within 4 weeks;
• 17.The live vaccine was administered less than 4 weeks prior to study administration or possibly during the study period;
• 18.Have a history of mental illness or psychiatric substance abuse;
• 19.The subject cannot or does not agree to bear the cost of the self-paid portion of the examination and treatment, except for the clinical study drug, combined chemoradiotherapy, and SAE associated with the clinical study drug;
• 20.Other patients whom the medical practitioner considers inappropriate for inclusion.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 1 patient group

Total neoadjuvant therapy

Experimental group

Description:

The patients would receive neoadjuvant chemoradiotherapy treatment firstly. And then evaluated efficacy according to RECIST 1.1. If patients with cCR would receive surgery treatment after 4-6 weeks. After surgery, patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy alone treatment. If patients evaluated as PD, they would receive new treatment regimen after MDT discussed. Other patients with PR and SD would receive 2 cycles of neoadjuvant immunochemotherapy. And then, Efficacy of immunochemotherapy would be evaluated according to RECIST 1.1. For patients suitable for surgery, surgery should be performed after 4-6 weeks of immunotherapy. After surgery, the patients with R0 resection would divided into two groups, if patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy treatment. Other patients without R0 resection would receive new treatment regimen after MDT discussed.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Radiation: Neoadiuvant radiotherapy

Drug: Tirelizumab