S1 Plus Paclitaxel (IV&IP) Plus Bevacizumab (IP) Versus S1 Plus Oxaliplatin(IV) as First-line Treatment in Gastric or Gastroesophageal Junctional Adenocarcinoma With Malignant Ascites: An Open-label, Multicenter Phase II Study
试验速览
- 阶段
- 2 期
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Ascites response rate at 6 weeks
研究概览
简要总结
The purpose of this study is to compare the efficacy of S1 plus paclitaxel (intravenous injection & intraperitoneal injection) plus bevacizumab (intraperitoneal injection) vs. S1 plus oxaliplatin intravenous injection as first-line treatment in gastric or gastroesophageal junctional adenocarcinoma with malignant ascites.
详细描述
This is a prospective, open-label, multicenter clinical trial, to compare the efficacy of S1 plus paclitaxel (intravenous injection & intraperitoneal injection) plus bevacizumab (intraperitoneal injection) versus S1 plus oxaliplatin intravenous injection as first-line treatment in gastric or gastroesophageal junctional adenocarcinoma with malignant ascites. A total of 66 patients who are diagnosed with gastric or gastroesophageal junctional adenocarcinoma will be allocated to receive either S1 orally administration plus paclitaxel intravenous injection & intraperitoneal injection plus bevacizumab intraperitoneal injection, or to receive S1 orally administration plus oxaliplatin intravenous injection. The primary end point is ascites response rate at 6 weeks. The secondary end points include the median overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), objective response rate (ORR), puncture free survival, volume of drainage, the quality of life (QoL) and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years ≥ Age≤ 70 years, male or female
- •Pathologically confirmed adenocarcinoma of the gastric or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease; with medium amount of malignant ascites which can be catheterized.
- •Diagnostic criteria for malignant ascites (meet any of the following criteria): ascites cytology positive; or imaging or pathological confirmed peritoneal metastases.
- •No prior anti-tumor treatment to the metastatic disease; an interval of at least 6 months from the last adjuvant chemotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status( PS) score 0-
- •Normal major organ function, and laboratory tests must meet the following criteria: hemoglobin (HGB) ≥ 90 g/L, neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109/L, total bilirubin (TBil) ≤ 1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 UNL, serum creatinine (Cr) ≤ 1 UNL; creatinine clearance rate (CCr) ≥ 60 ml/min (calculated using the Cockcroft-Gault equation).
- •International Normalized Ratio (INR) ≤ 1.5 and partial prothrombin time (PPT) or activated partial thromboplastin time (APTT) ≤ 1.5 UNL within 7 days before enrollment.
- •Life expectancy of at least 12 weeks
- •Signed informed consent (ICF)
- •For women of child bearing potential, a negative serum or urine pregnancy test result should be obtained with 7 days before enrollment; Women of childbearing potential and men must agree to use adequate contraception before entering the program until at least 8 weeks after the last study drug administration.
排除标准
- •Known hypersensitivity or allergic to any of the study drugs, study drug classes, or excipients in the formulation.
- •Subject received chemotherapy to the metastatic disease (except adjuvant/neoadjuvant chemotherapy administered 24 weeks before enrollment)
- •Subject with other malignancies, except for non-melanoma skin cancer or in-situ cervical carcinoma under adequate treatment, or other treated malignancies without evidence of recurrent for 5 years.
- •Anti-tumor cytotoxic drug therapy within 14 days prior to enrollment（longer washout time interval might needed depends on drug characteristics）
- •Uncontrolled hypertension which cannot be reduced to normal range by antihypertensive agents [Systolic Blood Pressure(SBP) >140 mmHg, diastolic blood pressure (DBP) > 90 mmHg], coronary artery disease > grade 1, arrhythmia > grade 1 [including corrected QT(QTc) interval prolongation: QTc>450 ms for male，QTc>470 ms for female], grade 1 heart failure.
- •Proteinuria ≥ ++，or persistent proteinuria > 1.0 g/24 hours
- •Presence of any toxicity ≥ grade 1 according to NCI-CTCAE except for alopecia.
- •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks, cerebral hemorrhage、cerebral infarction), deep vein thrombosis and pulmonary embolism within 12 months before enrollment.
- •Bowel obstruction within 6 weeks before enrollment.
- •Surgical treatment was performed within 6 weeks before enrollment. Subject should recover from any major surgery.
- •Serious uncontrolled systemic illness or medical condition or uncontrolled infections, including but not limited to: uncontrollable ventricular arrhythmias, history of documented myocardial infarction within 3 months, uncontrollable epileptic dementia, unstable spinal compression, superior vena cava syndrome, extensive bilateral interstitial pulmonary disease by high-resolution computed tomography (HRCT), or any neurological or mental abnormalities which affect compliance.
- •Human immunodeficiency virus (HIV) positive
- •Pregnancy or lactation women
- •Cannot be orally administered medication
- •Subject with a tendency for gastrointestinal hemorrhage. Including: Black stool or hematemesis within 2 months; For subjects positive in occult test with unresected primary lesion, if the principle investigator in each center considers with possibility of gastrointestinal hemorrhage, the subject could not be enrolled.
- •Subject with malignant pleural effusion need medical intervention.
- •A history or evidence of hereditary hemorrhagic constitution or coagulation disorder that increases the risk of bleeding
- •Subjects with central nerve system metastases
- •Have been enrolled in other clinical trial with investigational drug treatment within the 4 weeks of start of study treatment
- •For subject with bone metastases, palliative radiotherapy was given 4 weeks before enrollment (radiation field >5%).
- •Any other disease or condition that the investigator considers not suitable for participating in this clinical trial.
研究组 & 干预措施
Experimental arm
S1+Paclitaxel (IV&IP)+Bevacizumab (IP)
干预措施: S1 (Drug)
Experimental arm
S1+Paclitaxel (IV&IP)+Bevacizumab (IP)
干预措施: Paclitaxel (Drug)
Experimental arm
S1+Paclitaxel (IV&IP)+Bevacizumab (IP)
干预措施: Bevacizumab (Drug)
Control arm
S1+Oxaliplatin (IV)
干预措施: S1 (Drug)
Control arm
S1+Oxaliplatin (IV)
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Ascites response rate at 6 weeks
时间窗: 6 weeks
response of ascites at 6 weeks
次要结局
- TTF(12 months)
- PFS(12 months)
- Adverse events(12 months)
- OS(2 years)
- ORR(12 months)
- Puncture free survival(12 months)
- Volume of drainage(12 months)
研究者
Yunpeng Liu
Director
China Medical University, China