A Phase II Study of Pazopanib in Combination With Capecitabine and Oxaliplatin (CAPEOX) in Patients With Advanced Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Response rate
研究概览
简要总结
In order to improve survival of metastatic gastric cancer patients, we plan to to conduct a phase II trial of CapeOx with 800 mg once-daily pazopanib as a first-line chemotherapy in metastatic gastric cancer patients.
详细描述
Despite improvements in the early diagnosis of gastric cancer, many patients present with inoperable disease and an effective, novel combination treatment is urgently needed for these patients population. A recent meta-analysis demonstrated that chemotherapy improves survival for patients with advanced gastric cancer compared with best supportive care alone [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.28-0.52] and that combination chemotherapy is superior to monotherapy (HR 0.83, 95% CI 0.74-0.93) (Wagner et al., 2006). For advanced gastric cancer, 5-FU in combination with cisplatin (FP regimen) is commonly used reference regimen, which are successfully replaced by capecitabine and oxaliplatin in recent phase III trial (Cunningham et al., 2008; Okines et al., 2009). In phase II trial, CAPEOX (capecitabine combined with oxaliplatin) regimen also showed promising activity for the metastatic gastric cancer (Park et al., 2006; Park et al., 2008). In order to improve survival of metastatic gastric cancer patients, various clinical trials incorporated novel molecularly targeted agent in combination with the reference arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who provide written informed consent
- •Age over 18 years
- •Histologically proven unresectable gastric cancer
- •ECOG performance status of 0-2
- •At least one uni-dimensionally measurable lesion by RECIST criteria ver 1.1
- •Adequate organ system function absolute neutrophil count > 1,500/µL, platelets > 100,000/µL, hemoglobin > 9g/dl Total bilirubin < 1.5 times upper limit of normal (ULN), AST and ALT < 2.5 times ULN, PT (INR), PTT < 1.2 times UNL Serum creatinine less than 1.5 mg/dL or Calculated Ccr at least 50 mL/min, Urine Protein to Creatinine Ratio (UPC) less than 1
- •female with Non-childbearing potential
排除标准
- •Prior malignancy
- •History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug
- •Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including
- •Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
- •Presence of uncontrolled infection
- •Corrected QT interval (QTc) above 480 msecs using Bazett's formula
- •History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina, Coronary artery bypass graft surgery, Symptomatic peripheral vascular disease, Class II or higher congestive heart failure
- •Poorly controlled hypertension while on antihypertensive agents
- •History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
- •Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
- •Evidence of active bleeding or bleeding diathesis
- •Hemoptysis within 6 weeks of first dose of study drug
- •Any serious and/or unstable preexisting medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
- •Unable or unwilling to discontinue use of prohibited medications listed in the protocol
- •Treatment with any of the following anti-cancer therapies;Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib; biologic therapy, immunotherapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib; No prior chemotherapy except adjuvant chemotherapy (Patients who received adjuvant chemotherapy at least 6 months prior to study entry will be allowed regardless of chemotherapeutic regimen
- •Pre-existing grade 2 (or higher) motor or sensory neuropathy by CTCAE v4.0
- •Known allergy to study drugs
研究组 & 干预措施
Pazopanib in combination with capecitabine and oxaliplatin
Capecitabine 850 mg/m2 bid on day 1-14, Oxaliplatin 130 mg/m2 IV on day 1 and Pazopanib 800 mg once in a day on day 1-21, every 3 weeks
干预措施: Pazopanib in combination with capecitabine and oxaliplatin (Drug)
结局指标
主要结局
Response rate
时间窗: 6 months after last patient
次要结局
- Toxicities(6 months)
- Progression free survival (PFS)(one year)
- Overall survival (OS)(Two years)
- Metabolic response rate by PET-CT(1 month)
研究者
Joon Oh Park
associate professor
Samsung Medical Center