Sequential Preoperative Penpulimab Combined With Chemoradiotherapy(CRT) for Locally Advanced Esophageal Squamous Cell Cancer

Study Overview
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Brief Summary
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This study used an open single center study design to observe the efficacy and safety of Penpulimab combined with Chemoradiotherapy(CRT) in preoperative T2,3,4aN0-1-2M0 esophageal squamous cell carcinoma (ESCC).

Official Title
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Sequential Preoperative Penpulimab Combined With Chemoradiotherapy(CRT) for Locally Advanced Esophageal Squamous Cell Cancer: A Prospective, Single Arm, Single Center，Exploratory Study

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Penpulimab Combined With CRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Resectable t2,3,4an0-1-2m0 esophageal squamous cell carcinoma initially diagnosed by histology or cytology; Without any systematic anti-tumor treatment; ECOG 0-1; ANC≥ 1.5×109/L; PLT≥ 75×109/L; HB≥ 8.0 g/dL; TBIL ≤ 1.5´ ULN; ALT and AST ≤ 2.5´ULN; Cr ≤ 1.5´ULN or CCr ≥ 60ml/min; Urine protein < +, if urine protein + then the total protein in 24 hours must be <500mg; Blood glucose is within the normal range and / or patients with diabetes are in treatment, but blood glucose is controlled in a stable state; FEV1 ≥ 2L; If the baseline FEV1 is less than 2L, it is estimated that the FEV1 after surgery is greater than 800ml； No myocardial infarction within 1 year; No unstable angina pectoris; No symptomatic severe arrhythmia; No cardiac insufficiency； There are no serious complications or other major diseases that have not been cured； Thoracic surgeons judge those who can tolerate the operation； Female subjects with fertility and male subjects with partners of childbearing age need to use a medically approved contraceptive measure during the study treatment and at least 6 months after the last chemotherapy； The subjects voluntarily joined the study and signed the informed consent form Exclusion Criteria: Received any kind of systematic anti-tumor treatment before the first use of the study drug； At the same time, another clinical study will be included, unless it is an observational (non intervention) clinical study； Subjects who need to be given corticosteroids (more than 10mg prednisone equivalent dose per day) or other immunosuppressants for systematic treatment within 2 weeks before the first use of the study drug； Have been vaccinated with tumor vaccine or have been vaccinated with live vaccine within 4 weeks before administration； Have a history of active autoimmune diseases and autoimmune diseases; Except for patients who have recovered from childhood asthma / allergy and do not need any intervention after adulthood; Autoimmune mediated hypothyroidism treated with a stable dose of thyroid hormone replacement; Use a stable dose of insulin for type I diabetes； Serious interference occurred within 4 weeks before the first use of the study drug (CTC AE>2); Baseline chest imaging examination showed active pulmonary inflammation, symptoms and signs of infection within 2 weeks before the first use of the study drug, or the need for oral or intravenous antibiotics； Have a history of interstitial lung disease； The subjects had active hepatitis B (HBV DNA ≥ 2000 IU/ml or 104copies/ml), hepatitis C (hepatitis C antibody positive and HCV-RNA higher than the lower limit of the analysis method); Pregnant or lactating women; There are serious complications or other major diseases that have not been cured; Patients judged by thoracic surgeons to be intolerant of surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Penpulimab Combined With Chemoradiotherapy(CRT)<br> | Drug: Penpulimab Combined With CRT<br>* Penpulimab: 200mg, intravenous infusion, once every two weeks. After completing two courses of CRT, continue to send Penpulimab 200mg every two weeks on the first and 14th days after the completion of CRT, two courses of treatment, a total of four courses. Radiotherapy 40gy/20fx, once a day from Monday to Friday, completed in 4 weeks; PC regimen: Paclitaxel 50mg/m2, intravenous drip, carboplatin AUC=2mg/ml/min, intravenous drip, once a week during radiotherapy, a total of 4 courses, the specific time is D1, 8, 15, 22 days after the beginning of radiotherapy. Gastrointestinal reactions such as nausea and vomiting should be routinely prevented before chemotherapy. Dexamethasone 10mg should be used 30   60 minutes before paclitaxel, and intramuscular injection should be stopped immediately in case of drug or infusion reactions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete remission（pCR）rate | Proportion of subjects who achieved pathological complete remission (PCR)，PCR was defined as the microscopic absence of tumor cells in the pathological evaluation of excised esophageal cancer lesions and regional lymph node samples after surgery. | 3 to 4 months | 
| safety（AE or SAE） | Incidence of adverse events or serious adverse events | 2 to 3 years from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor regression grade（TRG） | Evaluation of the focus of primary tumor after radiotherapy and chemotherapy | 3 to 4 months | 
| R0 resection rate | Proportion of subjects reaching R0 resection. resection was defined as no tumor cells remained within 1mm of the two cutting edges of the esophageal cancer lesions removed during the operation. | 3 to 4 months | 
| Event free survival（EFS） | Date of first administration to date of first recording of relevant events | 2 to 3 years from baseline | 
| Overall survival（OS） | Date of first administration to date of death due to any cause | 2 to 3 years from baseline | 
| Disease free survival（DFS） | Date from the operation to the first recording of relevant events | 2 to 3 years from baseline |