A Phase II Trial of RAD001 (Everolimus) for 2nd Line Treatment After Failure of Fluoropyrimidine Plus Platinum Chemotherapy in Patients With Metastatic or Recurrent Gastric Cancer With pS6 Ser 240/4 Expression
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- 4-month progression-free survival
研究概览
简要总结
This is a phase II study to evaluate RAD001 (Everolimus) in terms of 4-month progression-free survival rate (primary end-point) and response rate, toxicity, overall survival and biomarker assessment (secondary end-points) in patients with metastatic or recurrent gastric cancer with pS6 Ser 240/4 expression.
Eligibility criteria include pathologically proven non-resectable adenocarcinoma of stomach with measurable disease who failed previous first-line palliative chemotherapy including fluoropyrimidine and platinum with high expression of pS6 Ser 240/4.
Oral RAD001 (everolimus) 10mg daily will be administered and the dose will be adjusted according to the observed clinical toxicities. Treatment will be continued until disease progression or patient's intolerability to the study drug.
A study requires 40 assessable subjects to decide whether the proportion of patients who are free from progression at 4 months (16 weeks), P, is less than or equal to 0.1 or greater than or equal to 0.25 with a target error rate of 0.05 and β of 0.2. If the number of responses is 7 or less, the hypothesis that P >= 0.250 is rejected with a target error rate of 0.200 and an actual error rate of 0.182. If the investigators assume that drop-out rate is 10%, total accrual patient will be 45.
详细描述
Methodology: Prospective, non blinded, open label, single center phase II study
Criteria for evaluation: Assessment of response will be assessed radiologically according to RECIST criteria after completion of the two cycles. Evaluation will be by physical examination, chest X-ray, abdomen-pelvis CT scan Safety criteria: Physical examination, vital signs, performance status, CBC, serum chemistry, NCI CTC V.3.0
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
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histologically or cytologically documented stomach adenocarcinoma including adenocarcinoma of the esophagogastric junction
- •non-resectable disease by metastasis or recurrent disease after curative surgical resection (See Appendix A) with uni-dimensionally measurable disease
- •failure of 1st line chemotherapy including fluoropyrimidine (capecitabine, S1, or 5-FU,) and platinum (cisplatin or oxaliplatin) in palliative setting; progression during or within 6 months after chemotherapy
- •High expression of pS6 Ser 240/4 (proportion of pS6 Ser 240/4 positive cancer cells by immunohistochemistry > 10%)
- •Age 20 to 75 years old
- •Estimated life expectancy of more than 3 months
- •ECOG performance status of 2 or lower
- •Adequate bone marrow function
- •Adequate kidney function
- •Adequate liver function
- •Fasting serum cholesterol ≤ 300 mg/dL AND fasting triglyceride ≤ 2.5 X ULN
- •No prior radiation therapy to more than 25% of BM
- •psychological, familial, sociological or geographical conditions which do not permit medical follow-up and compliance with this study
- •Women of childbearing potential must have a negative pregnancy test on admission
- •Written informed consent
排除标准
- •Other tumor type than adenocarcinoma
- •CNS metastases or prior radiation for CNS metastases
- •Gastric outlet obstruction or intestinal obstruction
- •Evidence of active gastrointestinal bleeding
- •Bone lesions as the sole evaluable disease
- •Past or concurrent history of neoplasm other than stomach cancer
- •Pregnant or lactating women, women of childbearing potential not employing adequate contraception
- •Other serious illness or medical conditions
- •Concomitant or with a 4-week period administration of any other experimental drug under investigation
- •Concomitant chemotherapy, hormonal therapy, or immunotherapy
- •Any preexisting medical condition of sufficient severity to prevent full compliance with the study
研究组 & 干预措施
RAD001 (everolimus)
干预措施: RAD001 (Drug)
结局指标
主要结局
4-month progression-free survival
时间窗: up to 3years
Progression-free survival is defined as the time from the first treatment to the onset of progressive disease per RECIST criteria or to the date of death whichever comes first. For patients who do not experience progressive disease or death, the progression-free survival duration will be right censored on the last disease assessment date.
次要结局
- Response rate(Up to 1year)
- Biomarker assessment(24months)
- Overall survival(Up to 3years)
- Number of participants with adverse events(Monitoring of adverse events will be contineud for at least 28days following the last dose of study treatment)
研究者
Yoon-Koo Kang
Professor
Asan Medical Center