Clinical trial NCT05189730: Selected Chemotherapy Combined Immunotherapy Treated High Risk Patient After NCRT in Resected Locally Advanced ESCC
Official title: Selected Chemotherapy Combined Immunotherapy Treated High Risk Patient After Neoadjuvant Chemoradiotherapy in Resected Locally Advanced Esophageal Squamous Cell Carcinoma: an Exploratory Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: neoadjuvant treatment
immunotherapy
chemoradiotherapy
Lead sponsor: Sichuan Cancer Hospital and Research Institute
Sponsor class: OTHER
First posted: 2022-01-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Complete pathologic response rate
timeFrame: 3 months
measure: Incidence of adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Clinical Complete Remission
timeFrame: 3 months
measure: Major Pathological Remission rate
timeFrame: 3 months
measure: Objective Remission Rate
timeFrame: 3 months
measure: Rate of R0 resection
timeFrame: 3 months
measure: Events Free Survival
timeFrame: Through study completion, an average of 1 year.
measure: Overall Survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan Cancer Hospital and Research Institute
state: Sichuan
Study officials:
References:
citation: He W, Wang C, Wu L, Wan G, Li B, Han Y, Li H, Leng X, Du K, Chen H, Wang Q, Peng L. Tislelizumab Plus Chemotherapy Sequential Neoadjuvant Therapy for Non-cCR Patients After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ETNT): An Exploratory Study. Front Immunol. 2022 Jun 2;13:853922. doi: 10.3389/fimmu.2022.853922. eCollection 2022.