REGORAFENIB AFTER FAILURE OF GEMCITABINE AND PLATINUM-BASED CHEMOTHERAPY FOR LOCALLY ADVANCED (NON RESECTABLE) AND METASTATIC INTRA-HEPATIC OR HILAR CHOLANGIOCARCINOMA: A Randomized Double-blinded Phase II Trial.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 66
- 试验地点
- 12
- 主要终点
- Improve median PFS
研究概览
简要总结
The study is a multicenter randomized (1:1) placebo-controlled, double-blinded phase II trial aiming to demonstrate an improvement of median PFS when treating locally advanced unresectable or metastatic patients suffering from an intra-hepatic or hilum (mass-forming) cholangiocarcinoma with Regorafenib as compared to placebo, and after progression after GEM-CDDP (or GEM-OX), or gemcitabine alone followed or preceded by platinum (CDDP or oxaliplatin)-based chemotherapy.
The principal objective is to investigate Regorafenib efficacy by prospectively evaluating the PFS after the administration of Regorafenib combined with BSC as compared to placebo with BSC. Hypothesis is a 50% improvement in median PFS (from 6 weeks to 12 weeks in Regorafenib group).
详细描述
The principal objective is to investigate Regorafenib efficacy by prospectively evaluating the PFS after the administration of Regorafenib combined with BSC as compared to placebo with BSC. Hypothesis is a 50% improvement in median PFS (from 6 weeks to 12 weeks in Regorafenib group).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •histologically proven intra-hepatic or hilum cholangiocarcinoma (mass forming, not "liniting" tumor), locally advanced unresectable or metastatic
- •progression documented after GEM-CDDP (or GEM-OX), or gemcitabine alone followed or preceded by platinum-based (CDDP or oxaliplatin) chemotherapy
- •age > 18 years
- •ECOG PS 0/1 at study entry
- •measurable disease according to RECIST version 1.1
- •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirementsconducted within 7 days of starting to study treatment:
- •oSerum creatinine <1.5x upper reference range
- •oTotal bilirubin <1.5x ULN
- •oAlanine transaminase (ALT) and aspartate aminotransferase (AST) < 2.5x ULN (<5x ULN forpatients with liver involvement of their cancer).
- •oAmylase and lipase <1.5x ULN.
- •life expectancy of at least 12 weeks
- •effective contraception for both male and female patients if the risk of conception exists
- •negative proteinuria on dipstick or 24 hours proteinuria<1000mg
- •signed written informed consent
排除标准
- •unability to take oral medication
- •any malabsorption condition
- •patients taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg. Clarithromycin, indinavir,itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin,voriconazole) or strong CYP3A4 inducers (eg. Carbamazepine, phenobarbital, phenytoin, rifampin, St-John's Wort) (see section 8)
- •persistent proteinuria >3.5g/24 hours measured by urine protein-creatinine ratio from a random urinesample (persistent proteinuria >3 non-healing woud, ulcer, or bone fracture
- •any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of studymedication
- •interstitial lund disease with ongoing signs and symptoms at the time of informed consent
- •uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
- •history of myocardial infarction, deep venous or arterial thrombosis, cerebrovascular accident (CVA) during the last 6 months
- •previous exposure to anti-VEGF targeting therapy (including Regorafenib) and to signal transduction inhibitors
- •known hypersensitivity to any of the components of study treatments
- •previous malignancy in the last past 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
- •pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods
- •medical or psychological conditions that would not permit the patient to complete the study or sign inform consent
- •unstable angina, congestive heart failure ≥NYHA class II
- •uncontrolled hypertension despite optimal management (systolic blood pressure >150 mmHg or diastolic pressure > 90mmHg)
- •pheochromocytoma
- •HIV infection
- •active chronic hepatitis B or C with a need for antiviral treatment
- •liver failure, cirrhosis Chil Pugh B or C
- •brain metastasis
- •major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment
- •intra-hepatic locoregional therapy (DC Beads, SIRT)
- •history of organ allograft
- •ongoing infection
- •renal failure requiring dialysis
- •patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study
研究组 & 干预措施
Regorafenib/active
Subjects randomized to be treated with Regorafenib (active product) will receive once a day 160 mg po (four tablets of 40 mg) for 3 weeks of every 4 weeks cycle (3 weeks on and 1 week off). Duration of one cycle is 28 days.
干预措施: Regorafenib/active (Drug)
Regorafenib/placebo
Subjects randomized to be treated with Regorafenib (placebo) will receive once a day 160 mg po (four tablets of 40 mg) for 3 weeks of every 4 weeks cycle (3 weeks on and 1 week off). Duration of one cycle is 28 days.
干预措施: Regorafenib/placebo (Drug)
结局指标
主要结局
Improve median PFS
时间窗: 6 to 12 weeks
The primary endpoint is to improve median PFS from 6 weeks to 12 weeks in Regorafenib group.
次要结局
- Correlation between dynamic tumor response rate and metabolic response rate(At cycle 1 day 15)
- Evaluation of response rate(At pretreatment visit (14 to 1 days before treatment initiation), every 6 weeks for 3 times then every 8 weeks until progression)
- Correlation between radiologic response rate and "Dynamic tumor response rate"(At day 1 (pre-treatment) and day 15 of cycle 1)
- Correlation between radiological response and metabolic response(At pretreatment visit (14 to 1 days before treatment initiation))
- Evaluation of Overall Survival (OS)(After 1 year (March 2015))