Phase 1/2 Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins1 个研究点分布在 1 个国家目标入组 23 人开始时间: 2011年12月27日最近更新: 2020年1月22日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
入组人数: 23
试验地点: 1
主要终点: Phase I - Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy as Measured by Number of Participants Who Tolerated the Maximal Dose of LDE-225

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is an open-label phase 1/2 study that will combine the chemotherapy agents gemcitabine and nab-paclitaxel with an oral hedgehog inhibitor LDE225 (Sonidegib). The objective is to assess tolerability and the resection rate of patients with borderline resectable pancreatic adenocarcinoma who use this treatment.

详细描述

The investigators propose treating 6-12 patients during the phase 1 portion and 40 patients in the phase 2 stage.

Phase 1 Stage:

Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with escalating doses (400mg, or 600mg, or 800mg) of LDE-225. After completion of neoadjuvant therapy, the subjects will receive combined chemotherapy and radiation. Then subjects who are eligible for resection will go ahead with surgery. Following resection, subjects will complete two additional cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 in combination with LDE-225.

Phase 2 Stage: In the Phase 2 stage the patients will be randomized to receive gemcitabine and nab-paclitaxel with or without the hedgehog inhibitor LDE225:

Arm A: Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose.
Arm B: Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m on days 1, 8 and 15.

研究设计

研究类型: Interventional
分配方式: 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

•Histologically or cytologically confirmed adenocarcinoma of the pancreas.
•Must have borderline resectable pancreatic adenocarcinoma
•Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
•No previous radiotherapy, surgery, chemotherapy or investigational drug therapy.
•Age >18 years
•Life expectancy of greater than 1 month.
•ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
•Adequate organ and marrow function
•Asymptomatic for jaundice and ascites. Pain symptoms should be stable.
•Negative serum pregnancy test
•Sexually active males should agree to use a barrier form of contraception, even if they have had a vasectomy, during the study and for 6 months after stopping LDE
•Males should not donate sperm during treatment, and for up to six months after last dose. Sexually active females of child bearing potential agree to using highly effective contraception during study and for 20 months after final dose of LDE
•Agree not to donate blood products for 12 months after stopping LDE
•Willing to have two biopsies while on treatment for correlative studies.

排除标准

•Patients who have had previous radiotherapy, surgical resection, chemotherapy or investigational drug therapy for pancreatic adenocarcinoma.
•Patient has known metastatic disease.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to LDE225 or other agents used in the study.
•Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
•Uncontrolled illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure not controlled with medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
•Pregnant women are excluded
•Patient has undergone a major surgery, other than diagnostic surgery within four weeks prior to starting treatment on this study.
•Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE
•Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE
•Patients with neuromuscular disorders.
•Patients with impaired cardiac function.

研究组 & 干预措施

Phase I-Gem,nab-paclitaxel,LDE225-600mg

Experimental

Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily.

干预措施: LDE225-600mg (Drug)

Phase I-Gem,nab-paclitaxel,LDE225-600mg

Experimental

Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily.

干预措施: Gemcitabine (Drug)

Phase I-Gem,nab-paclitaxel,LDE225-600mg

Experimental

Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily.

干预措施: nab-paclitaxel (Drug)