Eligibility |
Inclusion Criteria:
- (1) patients with esophageal squamous cell carcinoma within pT1 (stage pT1N0M0)
confirmed by pathology;
- (2) The following conditions were confirmed by pathology after ESD: submucosal
invasion > 200µm (stage SM2-SM3), undifferentiated or poorly differentiated
pathological degree, positive surgical margin, vascular and lymphatic invasion;
- (3) aged 18-75 years old (inclusive);
- (4) predicted survival time =6 months;
- (5) ECOG score of 0-1;
- (6) no obvious other symptoms or no effect assessed by researchers;
- (7) Women of childbearing potential must have a negative serum pregnancy test within 7
days before the first dose. Male or female patients of childbearing potential
volunteered to use an effective contraceptive method, such as dual barrier methods,
condoms, oral or injectable contraceptives, intrauterine devices, etc., during the
study and for 90 days after the last study medication was taken. All female patients
will be considered fertile unless the woman has undergone natural menopause,
artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnexectomy);
- (8) Electrocardiogram, blood, biochemical and other basic examinations had no
contraindications to radiotherapy, and had sufficient bone marrow, liver and kidney
organ functions. Laboratory examinations within 7 days before the first dose of
medication met the following requirements: a. Absolute neutrophil count (ANC)
=1.5×109/L, platelet =100×109/L and hemoglobin =90g/L (no blood transfusion, blood
products, granulocyte colony-stimulating factor or other hematopoietic stimulating
factor correction within 14 days before laboratory tests); b. Serum total bilirubin
=1.5 times the upper limit of the normal reference range (× ULN); c. alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) =1.5 × ULN; d. Serum
creatinine =1.5 × ULN and creatinine clearance =50 mL/min, (calculated by
Cockcroft/Gault formula) : Female: Ccr= (140-age) x weight (kg) x 0.85/(72 x serum
creatinine (mg/dL)) Male: Ccr= (140-age) x body weight (kg) x 1.00 /(72 x serum
creatinine (mg/dL)); e. Urine routine examination showed urine protein < 2+; If
urinary protein is =2+, 24-hour urinary protein should be less than 1 g; f. Sufficient
coagulation function, international normalized ratio (INR) =1.5, prothrombin time
(PT), activated partial prothrombin time (APTT) =1.5 × ULN; If the subject is
receiving anticoagulant therapy, as long as the PT is within the prescribed range of
anticoagulant drugs;
- (9) patients who know all available treatment options and understand the advantages
and disadvantages of each option and are willing to enroll after being fully informed;
- (10) consent to provide tissue examination specimens for further confirmation of
pathological grade if necessary;
- (11) Suitability for inclusion in the study was determined by two physicians with
senior professional titles or above independently;
- (12) have fully understood and voluntarily provided informed consent for the study
(prior to any trial-specified procedures) and be able to comply with
protocol-specified visits and related procedures.
Exclusion Criteria:
- (1) growth period on contraception, pregnancy (test positive for drug use before
pregnancy) or lactating women;
- (2) patients currently have any disease or condition affect drug absorption, or
patients cannot oral medicine;
- (3) patients with other malignant tumors (except well-controlled basal cell or
squamous cell carcinoma of the skin, carcinoma in situ of the cervix, non-melanoma
skin cancer, or lentigo malignant nevus) within the past 5 years or with concurrent
systemic malignant tumors;
- (4) Patients with other chronic diseases had contraindications to radiotherapy;
- (5) the presence of any active autoimmune disease requiring systemic treatment or a
history of autoimmune disease within the past 2 years, including but not limited to
interstitial pneumonia, uveitis, inflammatory bowel disease, hepatitis, hypophysitis,
vasculitis, systemic lupus erythematosus, etc. (vitiligo, psoriasis, alopecia, or
Graves' disease without systemic treatment within the past 2 years; Only need insulin
replacement therapy of patients with type 1 diabetes can be incorporated into); Known
primary immunodeficiency disease; For patients with only positive autoimmune
antibodies, the presence of autoimmune diseases should be determined according to the
investigator's judgment;
- (6) receiving systemic immunostimulant therapy within 4 weeks before the first dose;
- (7) administration of any live or live attenuated vaccine within 4 weeks before the
first dose or planned during the study period;
- (8) patients who underwent major surgery (the definition of major surgery referred to
grade 3 and grade 4 surgery specified in the "Administrative Measures for the Clinical
Application of Medical Technology" implemented on May 1, 2009) or unhealed wounds,
ulcers or fractures within 4 weeks before the first medication;
- (9) Patients had drug-uncontrolled hypertension defined as systolic blood pressure
=140 mmHg and/or diastolic blood pressure =90 mmHg;
- (10) patients with active gastric and duodenal ulcer, ulcerative colitis and other
gastrointestinal diseases, or unresected tumors with active bleeding, or other
conditions that may cause gastrointestinal bleeding or perforation as judged by the
investigators;
- (11) for the first time 2 months before using this drug has a history of thrombosis or
bleeding tendency obviously evidence or patients (> 30 mL, 2 months bleeding appear
hematemesis, black dung, bloody), haemoptysis > 5 mL (4 weeks) of fresh blood, PICC
except caused by blood clots;
- (12) for the first time happened within six months before using this drug arterial
thrombosis or deep vein thrombosis; Or had a stroke event and/or transient ischemic
attack within 12 months;
- (13) clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction, severe/unstable angina, or coronary artery bypass grafting
within 6 months before the first dose of medication; Congestive heart failure (New
York heart association (NYHA) class 2 or higher. Left ventricular ejection fraction
(LVEF) <50%;
- (14) any arterial thromboembolic event, including myocardial infarction, unstable
angina, cerebrovascular accident, or transient ischemic attack, occurred within 6
months before enrollment;
- (15) History of deep vein thrombosis, pulmonary embolism, or any other major
thromboembolism within 3 months before enrollment (superficial venous thrombosis was
not considered a "major" thromboembolism);
- (16) patients with active tuberculosis (TB), is receiving anti-tuberculosis treatment
or medication for the first time 1 year before received anti-tuberculosis treatment;
- (17) patients with previous or current history of pulmonary fibrosis, interstitial
pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe
impaired pulmonary function, etc.;
- (18) the known history of allogeneic organ transplantation and the history of
allogeneic hematopoietic stem cell transplantation;
- (19) patients with active infection occurred prior to or during the screening, first
radiotherapy fever of unknown origin (temperature > 38.5 oC);
- (20) clinically significant severe electrolyte abnormalities as judged by the
investigator;
- (21) significant malnutrition, such as need intravenous supplement nutrient solution;
The exception was correction of malnutrition for more than 4 weeks before the first
treatment;
- (22) The patient had uncured hyperthyroidism;
- (23) other acute or chronic medical conditions, psychiatric conditions, or abnormal
laboratory values that could increase the risk associated with the study treatment or
interfere with the interpretation of the study results and would, in the
investigator's judgment, have made the patient ineligible for the study;
- (24) uncontrolled metabolic disorders or other non-malignant organ or systemic
diseases or secondary effects of cancer, and may lead to high medical risk and/or
uncertainty in the evaluation of survival;
- (25) The investigator considered that the patient was not suitable to participate in
the study for other reasons.
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