Esophageal Neoplasms
Conditions
Brief 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
Interventions
DRUGPaclitaxel + Cisplatin + TQB2450 injection+ Anlotinib
TQB2450 injection: 1200 mg, i.v.gtt , d1;Anlotinib 10mg, po.qd , d1-14；Paclitaxel 135mg/m2, i.v.gtt , d1; Cisplatin 60-75mg/m2, i.v.gtt , d1-d3; The above schemes are repeated every three weeks. After 4-6 cycles, the regimen is changed to Anlotinib (10mg, po.qd , d1-14)+TQB2450 injection（1200 mg, i.v.gtt , d1）. The regimen is repeated every 3 weeks until the disease progresses.
DRUGPaclitaxel + Cisplatin + TQB2450 injection
TQB2450 injection: 1200 mg, i.v.gtt , d1;Paclitaxel 135mg/m2, i.v.gtt , d1; Cisplatin 60-75mg/m2, i.v.gtt , d1-d3; The above schemes are repeated every three weeks. After 4-6 cycles, the regimen is changed to TQB2450 injection（1200 mg, i.v.gtt , d1）. The regimen is repeated every 3 weeks until the disease progresses.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Henan Cancer Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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) \<50% of patients;live Severe infection that is sexual or uncontrolled;Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;poor diabetes control (fasting blood glucose (fbg)\>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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival (PFS， RECIST assessment) | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response (DOR) | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） |
| Progression-free survival (iPFS) | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） |
| Objective response rate (ORR) | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） |
| Disease control rate (DCR） | each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months） |
| Incidence of Treatment-related adverse Events | Through study completion, an average of 3 weeks |
Countries
China
Contacts
Primary ContactSuxia Luo, Doctor
Outcome results
None listed