A Controlled Clinical Study of Endostar/PD-1 Inhibitors Combined With PP as First-line Treatment for Advanced Non-squamous Cell Lung Cancer With Negative Driving Gene
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- progression-free survival(PFS)
研究概览
简要总结
A Controlled Clinical Study of Endostar/PD-1 Inhibitors Combined With chemotherapy(Carboplatin-Pemetrexed) as First-line Treatment for Advanced Non-squamous Cell Lung Cancer With Negative Driving Gene
详细描述
This study was a controlled clinical trial.A total of 170 patients with pathologically confirmed non-squamous NSCLC would be enrolled.Patients were randomly divided into two groups, with 85 in the group A and 85 in the group B.The group A was treated with endostar,sintilimab and chemotherapy(carboplatin-pemetrexed).The group B was treated with endostar and chemotherapy(carboplatin-pemetrexed).The efficacy and safety would be evaluated.The progression-free survival and overall survival would be analyzed.This data of this study might provide a more effective treatment for non-squamous NSCLC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients volunteered to participate in the study and signed the informed consent;
- •Age 18-75, both male and female;
- •Histologically or cytologically confirmed advanced or metastatic (stage III B, III C or IV) non-squamous NSCLC , and no mutation was detected in the driving gene.
- •At least one measurable lesion according to RECIST 1.1,which should not be treated locally, such as radiotherapy.
- •ECOG PS 0-1
- •Expected survival ≥ 3 months
- •Patients who never received systemic therapy in the past, including radiotherapy ,chemotherapy, targeted therapy and immunotherapy , or patients who relapsed more than 6 months after adjuvant chemotherapy.
- •The main organ functions accorded with the following criteria within 7 days before treatment:
- •(1)Blood routine examination ( without blood transfusion in 14 days): hemoglobin (HB) ≥ 90 g/L; neutrophil absolute value (ANC) ≥ 1.5 *109/L; platelet (PLT) ≥80 *109/L.
- •(2) Biochemical tests should meet the following criteria: 1) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); 2) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 *ULN, if accompanied by liver metastasis, ALT and AST ≤ 5* ULN; 3) serum creatinine (Cr) ≤ 1.5* ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;4) Serum albumin (≥35g/L).
- •(3) Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥the low limit of normal value (50%).
- •9 Tissue samples should be provided for biomarker analysis (such as PD-L1 ) Patients who could not provide new tissues could provide 5-8 paraffin sections of 3-5 μm by archival preservation.
排除标准
- •Severe allergic reactions to humanized antibodies or fusion proteins in the past
- •known to have hypersensitivity to any component contained in Endostar or antibody preparations;
- •Diagnosed of immunodeficiency or received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 14 days before the study, allowing physiological doses of glucocorticoids (≤10 mg/day prednisone or equivalent);
- •Patients with active, known or suspected autoimmune diseases. Patients with type I diabetes, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia). Patients who would not triggers can be included.
- •Serious heart disease, include congestive heart failure, uncontrollable high-risk arrhythmia, unstable angina pectoris, myocardial infarction, and severe valvular disease.
- •Patients treated targeted drugs such as bevacizumab, sunitinib, sorafenib, imatinib, famitinib, regiffenil, apatinib and anlotinib
- •Patients recieved systemic antineoplastic therapy, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or mitomycin C within 6 weeks before the grouping),recieved over-extended-field radiotherapy (EF-RT) within 4 weeks before the grouping or limited-field radiotherapy to evaluate the tumor lesions within 2 weeks before the grouping
- •Positive hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus antibody (HCV Ab), indicating acute or chronic infection.
- •Patients with active pulmonary tuberculosis (TB) infection judged by chest X-ray examination, sputum examination and clinical physical examination. Patients with active pulmonary tuberculosis infection in the previous year should be excluded even if they have been treated; Patients with active pulmonary tuberculosis infection more than a year ago should also be excluded unless the course and type of antituberculosis treatment previously were appropriate.
- •Patients with brain metastases with symptoms or symptoms controlling less than 2 months
- •Major surgical treatment, incision biopsy or significant traumatic injury were performed within 28 days before the grouping.
- •The imaging showed that the tumors had invaded important blood vessels or likely to invade important blood vessels and cause fatal massive hemorrhage during the follow-up period judged by researchers.
- •patients with any physical signs or history of bleeding; Patients with any bleeding or bleeding events ≥ CTCAE grade 3,unhealed wounds, ulcers or fractures within 4 weeks before grouping
- •Arteriovenous thrombosis occurred within 6 months, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis and pulmonary embolism.
- •The study is dangerous for patients judged by researcher, or patients who may affect the completion of the study.
研究组 & 干预措施
Experimental:group A
endostar,210 mg,CIV 72h,d1-d3; sintilimab,200mg,IV,d1; carboplatin,5/AUC,IV,d1; Pemetrexed,500mg/m2 ,IV,d1； 3 weeks for a cycle;4-6 cycles; after the treatment for 4-6 cycles,endostar plus sintilimab for maintenance therapy until PD or intolerable toxicity ;
干预措施: endostar/PD-1 inhibitor (Drug)
control:group B
endostar,210 mg,CIV 72h,d1-d3; carboplatin,5/AUC,IV,d1; Pemetrexed,500mg/m2 ,IV,d1； 3 weeks for a cycle;4-6 cycles; after the treatment for 4-6 cycles,endostar for maintenance therapy until PD or intolerable toxicity ;
干预措施: endostar (Drug)
结局指标
主要结局
progression-free survival(PFS)
时间窗: approximately 36 months
progression-free survival is defined as the time from enrollment to the date of first document disease progression or death from any cause
overall survival (OS)
时间窗: approximately 36 months
overall survival is defined as the time from randomization to death from any cause
次要结局
- objective response rate(ORR)(approximately 18 months)
- adverse event(AE)(approximately 36 months)
研究者
Dong Wang
chief physician
Third Military Medical University