Overview

This study is a two arm, randomized, prospective, multicenter study on the perioperative treatment of locally advanced resectable esophageal cancer with penpulimab combined with anlotinib hydrochloride and chemotherapy.

Eligibility

Inclusion Criteria:

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1. only those who meet all the following requirements can be enrolled in this trial: 1. age 18-75 years old, both male and female;

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       2. according to gastroscope / ultrasonic gastroscope biopsy, the pathology
          suggests esophageal cancer, and the clinical diagnosis is ct2n1-3m0 or
          ct3n0-3m0 or ct4n0-3m0, and the TNM stage is stage ii-iva;

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3. patients with non cervical esophageal cancer;

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       4. have not received previous systemic and local treatment for esophageal cancer
          according to RECIST 1 1 criteria at least one measurable lesion was used for
          imaging evaluation of neoadjuvant therapy;

• 5.ecog PS: 0-1 point;

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6. estimated survival ≥ 12 months;

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       7. the subject had no dysfunction of major organs, and the investigator assessed
          that the thyroid, lung, bone marrow, liver, kidney and heart functions were
          basically normal; 8. women of childbearing age must have taken reliable
          contraceptive measures or had a pregnancy test (serum or urine) within 7 days
          before enrollment, and the results are negative, and are willing to use
          appropriate methods of contraception during the test and - 8 weeks after the
          last administration of test drugs. For men, they must agree to use appropriate
          methods of contraception or have been surgically sterilized during the trial
          and 8 weeks after the last administration of the trial drug;

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       9. the subjects voluntarily joined the study, signed the informed consent, had
          good compliance, followed the planned schedule, actively cooperated with
          returning to the hospital for regular clinical follow-up and necessary
          treatment, and cooperated with regular blood and tissue sample acquisition.

Exclusion Criteria:

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1. 5 years of other malignant tumors, except for cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta (non invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];

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2. patients with ulcerative esophageal squamous cell carcinoma;

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3. patients with esophageal fistula or tracheal fistula;

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       4. those who are sensitive to anlotinib, pembrolizumab, albumin paclitaxel or
          oxaliplatin and excipients;

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       5. have a history of immune deficiency, including HIV positive or suffering from
          other acquired or congenital immune deficiency diseases, or have a history of
          organ transplantation;

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6. patients with any severe and / or uncontrolled disease, including:

1. Patients with unsatisfactory blood pressure control (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mmHg); 2) Myocardial ischemia or myocardial infarction of grade I or above; 3) Arrhythmia (including QT interval ≥ 480 MS) and grade I cardiac insufficiency; 4) Diabetes mellitus with poor blood glucose control (fasting blood glucose (FBG) >10mmol/l) or high-dose glucocorticoid treatment; 5) Active or uncontrolled severe infection; 6) Decompensated liver disease, active hepatitis B (HBV-DNA ≥ 104copies/ml or 2000iu/ml) or hepatitis C (hepatitis C antibody and HCV RNA positive) were all above the lower limit of the analysis method; 7) Hyperthyroidism and hypothyroidism; 8) Active tuberculosis.

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       7. unrelieved toxic reactions higher than CTCAE grade 1 due to any previous
          treatment, excluding hair loss;

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       8. esophageal cancer patients with active bleeding within 2 months of the primary
          lesion;

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       9. patients whose tumors have invaded the important blood vessels or are judged by
          the investigator to be very likely to invade the important blood vessels during
          the follow-up study and cause fatal massive hemorrhage;

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      10. patients with multiple factors affecting oral drugs (such as inability to
          swallow, chronic diarrhea, intestinal obstruction, etc.), but patients with
          dysphagia who can drink water, can take anlotinib after dissolving the
          particles;

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      11. the urine routine indicates that the urine protein is ≥ + +, and the 24-hour
          urine protein quantitation is confirmed to be >1.0 g;

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      12. received major surgical treatment, incision biopsy or obvious traumatic injury
          within 28 days before grouping;

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      13. abnormal coagulation function: inr>1.5 or prothrombin time (PT) >uln+4 seconds
          or APTT >1.5uln), with bleeding tendency or undergoing thrombolytic or
          anticoagulant therapy; Within 4 weeks before grouping, patients with any
          bleeding or bleeding events ≥ CTCAE grade 3 had unhealed wounds, ulcers or
          fractures;

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      14. Those who have had arterial / venous thrombotic events within 6 months, such as
          cerebrovascular accident (including transient ischemic attack), deep vein
          thrombosis and pulmonary embolism;

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15. pregnant or lactating women;

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16. patients with distant metastasis;

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17. patients with significant myelosuppression;

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18. have a history of mental illness or abuse of psychotropic drugs;

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      19. Patients who have participated in clinical trials of other drugs within 4
          weeks;

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      20. according to the judgment of the investigator, patients with concomitant
          diseases that seriously endanger the safety of patients or affect the
          completion of the study;

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21. the investigator believes that it is not suitable for inclusion.