A Phase I/II, Non-randomized, Multi-center, Dose-escalating, Two-stage Efficacy and Feasibility Study of the Combination of Everolimus and Capecitabine in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Phase I part: Assessment of dose limiting toxicity and maximum tolerated dose. II part: efficacy and feasibility. Primary endpoint of the study will be response rate.
研究概览
简要总结
In the investigators study the investigators combine everolimus, administrated twice daily at a fixed total dose of 10 mg continuously with capecitabine administered bid for 14 days followed by 7 days rest. In this study, capecitabine will be dose escalated.
详细描述
The results form preclinical studies suggest that mTOR inhibitors are promising drugs for the treatment of various types of cancer. Everolimus seems the most attractive mTOR inhibitor because of the favourable pharmacokinetic profile and possibility of oral administration. Based on preclinical findings, mTOR inhibitors may be more efficacious when used in a rational combination with other cancer regiments like cytostatic drugs. Indeed, several multiagent combinations are being investigated in clinical trials at the moment, and the results are promising.
In our study we combine everolimus, administrated twice daily at a fixed total dose of 10 mg continuously with capecitabine administered bid for 14 days followed by 7 days rest. In this study, capecitabine will be dose escalated. The first dose level of capecitabine is 500 mg/m2 twice daily. Three patients will be enrolled per dose level, starting at dose level 1. If one of the 3 patients develops dose-limiting toxicity at any dose level, 3 other patients will start at the same dose level. If 2 or more out of these 6 patients develop DLT, no further dose escalations will be performed. The MTD will be considered to be the dose given at the previous lower level. No intrapatient dose escalation will be applied.
Once the MTD of capecitabine is established, the phase II part of the study will start in which 25 patients with various malignancies will be enrolled to evaluate the efficacy and feasibility of the combination of everolimus and capecitabine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patients with histological or cytological confirmed malignancies
- •Measurable lesion according to RECIST criteria (only for the phase II part of the study)
- •ECOG / WHO performance status of 0-2
- •Age ≥ 18 years
- •Life expectancy of at least 3 months
- •Minimal acceptable safety laboratory values defined as:
- •WBC ≥ 3.0 x 109 /L
- •Platelet count ≥ 100 x 109 /L
- •Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALT or AST ≤ 2.5 x ULN, in case of liver metastases ≤ 5 x ULN
- •Renal function as defined by creatinine < 150μmol/L
- •Able and willing to give written informed consent
- •Able to swallow and retain oral medication
- •Able and willing to undergo blood sampling for pharmacokinetic and pharmacogenetic analysis
- •Mentally, physically and geographically able to undergo treatment and follow up.
排除标准
- •Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up
- •Women who are pregnant or breast feeding
- •Women of childbearing potential who refuse to use a reliable contraceptive method throughout the study
- •Serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
- •Any other medical condition that would interfere with study procedures and/or decrease safety of the protocol treatment
结局指标
主要结局
Phase I part: Assessment of dose limiting toxicity and maximum tolerated dose. II part: efficacy and feasibility. Primary endpoint of the study will be response rate.
时间窗: During treatment: assessments on day 1 every cycle (3 weeks). After treatment: every 3 months during the first 2 years, and every 6 months thereafter
Three patients will be enrolled per dose level, starting at dose level 1. If one of the 3 patients develops dose-limiting toxicity at any dose level, 3 other patients will start at the same dose level. If 2 or more out of these 6 patients develop DLT, no further dose escalations will be performed. The MTD will be considered to be the dose given at the previous lower level. No intrapatient dose escalation will be applied.
次要结局
- Time to treatment failure(Every 3 months during the first 2 years, and every 6 months thereafter.)
- Toxicity profile.(During treatment: assessments on day 1 every cycle (3 weeks). After treatment: every 3 months during the first 2 years, and every 6 months thereafter.)