tqb2450 solution for injection (tqb2450)+paclitaxel+cisplatin ± anlotinib in the treatment of esophageal cancer.

Conditions: Esophageal Neoplasms

Summary: the regimen of paclitaxel+cisplatin+tqb2450 injection combined or not combined with anlotinib is the first-line treatment of advanced esophageal squamous cell carcinoma. take pfs as the main evaluation index, the purpose is to evaluate its effectiveness and safety


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed squamous cell carcinoma of the esophagus, locally advanced, unresectable, recurrent or metastatic disease. * those who have not received systemic treatment before, or who relapsed after (new) adjuvant therapy/radical surgery more than 6 months ; note: including advanced or recurrent patients who ever received only radiotherapy on non-target lesions. the duration from the end of palliative treatment for local lesions (non-target lesions) to enrollment should \> 2 weeks; * according to recist 1.1, at least one measurable lesion; the measurable lesions should not have received local treatment such as radiotherapy (for the lesions in the area where received local radiotherapy, it can also be regarded as a target lesion if confirmed to progress according to the recist1.1); * 18 and 75 years old; * eastern cooperative oncology group (ecog) performance status of 0 to 1；life expectancy of at least 3 months. * the main organ function to meet the following criteria: (1)blood routine tests met the following requirements: a) haemoglobin(hb)≥90g/l ； b) absolute neutrophil count(neut)≥1.5×109/l ； c) platelet count(plt)≥100×109/l； （2） biochemical tests met the following requirements： total bilirubin(tbil)≤ 1.5 times the upper limit of normal (uln) .≤5 × uln if with liver involvement； serum creatinine ≤1.5 × the uln or creatinine clearance≥50ml/min。 （3） coagulation or thyroid function meet the following criteria: international normalized ratio (inr) ≤1.5 and partial thromboplastin time (pt) or activated ptt (aptt) ≤1.5 × (uln))." * male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study * the patient volunteers to participate in the study, signs a consent form, has good compliance, and obeys the follow-up, and is willing and able to follow the protocol during the study. exclusion criteria: * patients tends to have complete obstruction or patients requiring interventional treatment for obstruction; * patients with a high risk of bleeding or perforation due to the apparent invasion of adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed fistulas; * patients with symptoms of hematemesis, hematochezia and daily bleeding ≥ 2.5 ml, or any bleeding event with common terminology criteria for adverse events （ctcae） level 3 within 3 months before screening; * allergic to study drugs 、paclitaxel and cisplatin preparations or excipients; * adjuvant chemotherapy patients who have used paclitaxel or cisplatin, and relapse or metastasize within one year * a variety of factors affecting oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction); * patients with any severe and / or uncontrolled disease, including:unsatisfactory blood pressure control using antihypertensive drugs (systolic blood pressure ≥150 mmhg or diastolic blood pressure ≥100) mmhg) patients; patients with grade ≥ myocardial ischemia or myocardial infarction, arrhythmia (including qt interval ≥ 480ms); according to nyha criteria, iii-iv cardiac dysfunction, or cardiac ultrasonography prompted left ventricular ejection fraction (lvef) \ 10mmol/l);urine routine indicates that urine protein ≥ ++, and confirmed 24-hour urine protein quantitation \> 1.0 g * long-term unhealed wounds or fractures; * patients with active hemorrhage within 2 months of primary lesions; pulmonary hemorrhage with nci ctcae grade \>1, 4 weeks before of enrollment; other sites of bleeding nci ctcae grade \>2, 4 weeks before of enrollment; patients with bleeding tendency (such as active gastrointestinal ulcers) or patients undergoing thrombolytic or anticoagulant therapy such as warfarin, heparin or its analogues; * have undergone major surgery (craniotomy, thoracotomy or open surgery) within 4 weeks prior to the first dose study or major surgery is required during the study period. * a history of gastrointestinal perforation and/or fistula occurred within 6 months prior to treatment; or an overactive/venous thrombosis event such as a cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and lung embolism； * symptomatic central nervous system metastasis and/or cancerous meningitis are known to exist; * clinically significant ascites, including any ascites that can be found on a physical examination, ascites that has been treated or currently in need of treatment, and only those with a small amount of ascites but no symptoms can be selected; * a moderate amount of fluid in both sides of the chest, or a large amount of fluid in one side of the chest, or has caused respiratory dysfunction patient to be drained; * known to have active tuberculosis; * suffering from interstitial lung disease requiring steroid therapy; * uncontrolled metabolic disorders or other non-malignant tumors or systemic diseases or cancer secondary reactions that can lead to higher medical risks and/or survival evaluation of uncertainty; * significantly malnourished patients; * those who have a history of psychotropic substance abuse and are unable to quit or have a mental disorder; * a history of immunodeficiency, including a positive hiv test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation; * history of other primary malignancies, but the following : 1) complete remission of malignant tumors for at least 2 years prior to enrollment and no additional treatment during the study; 2) non-melanoma skin cancer or malignant freckle-like sputum with adequate treatment and no evidence of disease recurrence; 3) adequately treated and in situ carcinoma without evidence of disease recurrence; * female patients who are pregnant or breastfeeding; * according to the judgment of the investigator, there is a concomitant disease that seriously endangers the safety of the patient or affects the completion of the study.