A Randomized Phase II Trial of MEK Inhibitor Selumetinib (AZD6244) Combined Continuously or Sequentially With Cisplatin/Gemcitabine (CIS/GEM) Versus CIS/GEM Alone in Patients With Advanced Biliary Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Change in tumor size in millimetres
研究概览
简要总结
This is a phase II study (the second stage of testing a new drug or new drug combinations) to see how useful two different schedules of study drug selumetinib with cisplatin and gemcitabine are compared to cisplatin and gemticabine alone in patients with biliary cancer.
Selumetinib, an oral drug which plays an important role in the regulation of cell growth (MEK 1/2 inhibitor) has been shown to shrink tumours in patients with biliary cancer and other types of human cancers. Selumetinib has also been shown to shrink tumours when given in combination with cisplatin and gemcitabine in research studies done in animals and in some patients with biliary tract cancer. Cisplatin and gemcitabine are intravenous drugs that work by damaging DNA in tumor cells so that they are unable to grow and divide.
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
- 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
- •Unresectable, recurrent or metastatic, measurable biliary tract cancer or gall bladder cancer
- •No prior systemic therapy
- •Performance status 0, 1, or 2
- •Age 18 years or older
- •Estimated life expectancy > 3 months
- •Adequate hematological, liver, renal function
- •No evidence of active uncontrolled infection
- •Capable of giving written consent
- •Acceptable recovery of previous side effects
排除标准
- •Progressing within 3 or 6 months of receiving certain treatments
- •Prior chemotherapy for non-resectable or metastatic disease or a MEK inhibitor
- •Progressing within 6 months of adjuvant treatment.
- •May not have received prior chemotherapy for non-resectable/metastatic disease.
- •Prior MEK, RAS, or RAF inhibitors or history of hypersensitivity to study drugs.
- •Ampullary carcinoma
- •Incomplete recovery from previous surgery
- •Undergoing treatment with curative intent
- •Prior malignancy that could interfere with the response evaluation
- •Severe or uncontrolled systemic diseases or lab finding that makes it undesirable for patient to participate
- •Any psychiatric or other disorder likely to impact consent
- •Pregnant or breastfeeding
- •Patients with significant cardiac-related issues
- •History of eye-related issues.
- •Systemic disease, active infection, bleeding diatheses or renal transplant, including hep B, hep C or HIV
- •Receiving potent inhibitors or inducers of CYP3A4/5, CYP2C19 and CYP1A2 can continue with caution
研究组 & 干预措施
Arm C (Standard Care)
Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Gemcitabine (Drug)
Arm A (Continuous Dosing)
Run-In: Selumetinib, orally, BID for 7 days (Day -7 to Day -1)
On treatment: Selumetinib, orally, BID from Day 1-21 of every 28 day cycle. Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Selumetinib (Drug)
Arm A (Continuous Dosing)
Run-In: Selumetinib, orally, BID for 7 days (Day -7 to Day -1)
On treatment: Selumetinib, orally, BID from Day 1-21 of every 28 day cycle. Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Cisplatin (Drug)
Arm A (Continuous Dosing)
Run-In: Selumetinib, orally, BID for 7 days (Day -7 to Day -1)
On treatment: Selumetinib, orally, BID from Day 1-21 of every 28 day cycle. Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Gemcitabine (Drug)
Arm C (Standard Care)
Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Cisplatin (Drug)
Arm B (Sequential Dosing)
Run-In: Selumetinib, orally, BID for 5 days (Day -7 to Day -3) with 2 days washout
On treatment: Selumetinib, orally, BID from Day 1-5 and 8-19 of every 28 day cycle.
Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Selumetinib (Drug)
Arm B (Sequential Dosing)
Run-In: Selumetinib, orally, BID for 5 days (Day -7 to Day -3) with 2 days washout
On treatment: Selumetinib, orally, BID from Day 1-5 and 8-19 of every 28 day cycle.
Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Cisplatin (Drug)
Arm B (Sequential Dosing)
Run-In: Selumetinib, orally, BID for 5 days (Day -7 to Day -3) with 2 days washout
On treatment: Selumetinib, orally, BID from Day 1-5 and 8-19 of every 28 day cycle.
Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Change in tumor size in millimetres
时间窗: 10 weeks post initiation of therapy
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
次要结局
- Total rate of grade 3 and 4 toxicities(2 years)
- Number of participants with objective response and/or stable disease(6 months post initiation of therapy)
- Percentage of patients without progressive disease(10 weeks post initiation of therapy)
- Progression-free survival in months(Enrollment to disease progression or death)
- Overall survival in months(Time from enrollment to date of death)
- Total incidence of adverse events(2 years)