Phase I-II Study of bi-Weekly Fixed Dose Rate Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 4
- 主要终点
- Response
研究概览
简要总结
In Denmark approximately 200 new cases of cholangiocarcinoma are diagnosed every year. No standard treatment exists for patients with advanced cholangiocarcinoma, and improved systemic treatments are needed.
Duplets of gemcitabine, oxaliplatin and capecitabine have been evaluated in various cancers and several different regimens are well tolerated and active, especially in upper gastrointestinal cancers, exocrine pancreatic cancer and non-small cell lung cancer.
The triplet combination of these agents has not been studied, but a triplet combination of gemcitabine, oxaliplatin and 5-FU infusion has been evaluated in a phase I study.
Bi-weekly combination of gemcitabine and oxaliplatin has proven active and tolerable and warrants further study. In addition, fixed dose rate infusion of gemcitabine has shown interesting as the ability of mononuclear cells to accumulate gemcitabine triphosphate during therapy seems to be saturable.
We propose a phase I-II study of a bi-weekly schedule of gemcitabine, oxaliplatin and capecitabine. This regimen could be feasible in an out-patients setting.
The phase I part is a standard dose escalation study for patients with solid tumors. In the phase II part the recommended dose is studied in patients with advanced cholangiocarcinoma.
详细描述
Design
Open, non-randomized phase I/II study.
Purpose:
Phase I part To find MTD and RFTD for the combination of gemcitabine, oxaliplatin and capecitabine.
Dose Escalating Schedule Dose level Dose Gemcitabine 10 mg/m2/min 600-1000 mg/m2 day 1 and 14 Capecitabine p.o. x 2 daily. 1000-1250 mg/m2 day 1-7 and 14-21 Oxaliplatin 60-80 mg/m2day 1 and 14 Drugs: G C O Level 1 600 1000 60 Level 2 800 1000 60 Level 3 1000 1000 60 Level 4 1000 1250 60 Level 5 1000 1250 80 Level 6 1200 1250 80 Start level: Level 1, 3 patients per level
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven intra- or extrahepatic cholangiocarcinoma, papilla of the Vater or gallbladder carcinoma.
- •Age 18-75
- •Life expectancy > 12 weeks
- •Normal bone marrow function (neutrophiles > 1,5 x 109/l and platelets > 100 x 109/l)
- •Bilirubin < 1,5 x UNL
- •Transaminases < 3 x UNL
- •Normal renal function, Cr-EDTA clearance > 50 ml/min
- •No chemotherapy, radiotherapy or immunotherapy 4 weeks prior to inclusion
- •No known DPD-deficiency
- •No neuropathy
- •No uncontrolled, severe concurrent medical disease
- •Signed informed consent
排除标准
- •Chemotherapy, radiotherapy or immunotherapy 4 weeks prior to inclusion
- •Experimental therapy < 8 weeks prior to inclusion
- •Uncontrolled, severe concurrent medical disease
- •Prior malignancy during the last 5 years, except for non-melanoma skin cancer and carcinoma in situ cervix uteri.
- •Allergy to gemcitabine, oxaliplatin or capecitabine
- •Pregnancy or lactation
结局指标
主要结局
Response
次要结局
- Safety
- Time to progression
- SUrvival