A Phase Ib, Open-label, Multicenter, Dose-escalation, Safety and Tolerability Study of LDE225 in Combination With Gemcitabine in Patients With Locally Advanced or Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Incidence rate and category of dose limiting toxicities (DLTs)
研究概览
简要总结
This phase Ib study includes two phases: dose escalation phase and safety expansion phase.
During the dose escalation phase, successive cohorts of eligible patients (minimum 3 and maximum 6 evaluable patients per cohort) will receive increasing oral doses of LDE225 administered on a continuous once daily (QD) dose in combination of gemcitabine. This phase of the study will determine the maximum tolerated dose (MTD) and/ or recommended dose for expansion (RDE) of LDE225 administered in combination with gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma patients.
During the safety expansion phase, once the MTD of LDE225 is established, additional patients will be enrolled and treated at the MTD of LDE225 in combination with gemcitabine in order to further evaluate its safety, tolerability and explore the potential efficacy of the combined treatments on the patients in locally advanced or metastatic pancreatic adenocarcinoma.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with locally advanced or metastatic pancreatic adenocarcinoma that have not been previously treated or have progressed despite chemotherapy
- •Performance status of 0 or 1 per WHO classification
- •Adequate hematologic , renal and liver function
- •Adequate blood creatine kinase value (CK < 1.5ULN)
排除标准
- •Treatment with prior radiotherapy
- •Pancreatic cancer that is potentially curable by surgery
- •Women of childbearing potential unless they are using highly effective method of contraception Other protocol-defined inclusion/exclusion criteria may apply
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
LDE225+gemcitabine
Increasing doses of LDE225 (from 400 mg) once a day + 1000 mg/m2 of gemcitabine on days 1, 8 and 15 of every 28 day cycle.
干预措施: LDE225+gemcitabine (Drug)
结局指标
主要结局
Incidence rate and category of dose limiting toxicities (DLTs)
时间窗: first 8 weeks of study treatment
Dose limiting toxicities that occur during the first 8 weeks (56 days) of treatment with LDE225+gemcitabine. Dose limiting toxicity is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that meets study specific criteria.
次要结局
- Incidence rate of Adverse Events and Serious Adverse Events(at Informed Consent Form (ICF) sign off until 120 days after the last dose of study drug)
- Progression free survival(baseline, 8 weeks)
- Antitumor efficacy of LDE225+gemcitabine(baseline, week 9 of the study)
- Plasma pharmacokinetics(PK) parameters of LDE225(baseline, week 9 of the study)
- Plasma pharmacokinetics (PK) of gemcitabine(Baseline, week 9 of the study)
- Objective Response Rate(Baseline, 8 weeks)
- Serum tumor marker Ca 19-9(On Day 1 of every cycle (cycle = 28 days))
- Duration of Response(Baseline, 8 weeks)