此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

MEK Inhibitor MSC1936369B Plus FOLFIRI in Second Line K-Ras Mutated Metastatic Colorectal Cancer (mCRC)

2016年8月24日 更新者：EMD Serono

A Double-blind, Randomized, Comparative, Multicenter, Exploratory, and Placebo-controlled Phase II Trial of FOLFIRI Plus MSC1936369B or Placebo With a Safety run-in Part as Second-line Treatment of Metastatic K Ras Mutated Colorectal Cancer Subjects

The research trial is testing the experimental treatment pimasertib (MSC1936369B) in combination with FOLFIRI, as second-line treatment in metastatic K Ras mutated colorectal cancer subjects. The study will be run in two parts:

Part 1, or Safety Run-in Part: Will determine the maximum tolerated dose and the recommended Phase 2 dose (RP2D) of pimasertib combined with FOLFIRI as second-line treatment in subjects with metastatic K Ras mutated colorectal cancer.

Part 2 or Phase 2 Randomised Part: Will assess the anti-tumor activity of pimasertib combined with FOLFIRI compared to FOLFIRI with placebo as second-line treatment in metastatic K Ras mutated colorectal cancer subjects.

Phase I which Is an open label dose escalation "3+3" cohort, non-randomized, safety Phase II which is a double blind randomized safety/efficacy

研究概览

地位

终止

条件

干预/治疗

研究类型

介入性

注册 (实际的)

16

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

For Safety Run-in and Part 2 or Phase 2 Randomised Part

  • Histologically confirmed K-Ras mutated colon/rectum cancer
  • Subject's disease must have progressed during or after a first-line treatment for metastatic disease with oxaliplatin and fluoropyrimidines based chemotherapy with or without bevacizumab
  • Evidence of metastatic measurable disease at trial entry as per Response Evaluation Criteria in Solid Tumors. Complete tumor assessment performed within 14 days prior to first trial drug administration
  • Male/female subjects aged greater than or equal to (>=) 18 years
  • Subject has read and understood the informed consent form
  • Women of childbearing potential must have a negative blood pregnancy test at the screening visit. Subjects and their partners must be willing to avoid pregnancy during the trial

Exclusion Criteria:

For Safety Run-in and Part 2 or Phase 2 Randomised Part

  • Bone marrow impairment
  • Renal impairment
  • Liver function and liver cell integrity abnormality
  • History of central nervous system (CNS) metastases
  • History of difficulty of swallowing, malabsorption or other chronic gastrointestinal disease
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) greater than (>)1
  • Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B
  • Has received extensive prior radiotherapy on more than 30 percent (%) of bone marrow reserves, or prior bone marrow/stem cell transplantation
  • Has received chemotherapy, any investigational drug, or having participated in another clinical trial within the past 4 weeks prior to trial first drug administration
  • Has a history of any other significant medical disease
  • Past or current history (within the last 2 years prior to inclusion) of malignancies except for the indication under this study
  • Has significant cardiac conduction abnormalities and/or pacemaker
  • Is a pregnant or nursing female
  • Has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion
  • Other significant disease that in the Investigator's opinion would exclude the subject from the trial
  • Known hypersensitivity to the trial treatment(s) or diluents (when applicable), including placebo or other comparator drug(s)
  • Legal incapacity or limited legal capacity

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：双倍的

武器和干预

参与者组/臂
干预/治疗
实验性的：Part 1 or Safety Run-in Part: Pimasertib+FOLFIRI
药品：Pimasertib
Subjects will be administered with pimasertib orally once daily on Days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.
其他名称：
  • MSC1936369B
药品：FOLFIRI
Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter [mg/m^2] intravenous [i.v] infusion over 90 minutes or leucovorin [dl-leucovorin] 400 mg/m^2 i.v. infusion over 90 minutes; followed by irinotecan 180 mg/m^2 given as a 90-minute infusion in 500 milliliter [mL] dextrose 5%; followed by a bolus 5-fluorouracil [FU] 400 mg/m^2 and a 46-hour infusion 5-FU 2400 mg/m^2) at conventional doses on days 1 and 15 of the same 28 day cycle.
实验性的：Part 2 or Phase 2 Randomized part: Pimasertib+FOLFIRI
Planned, not performed
药品：Pimasertib
Subjects will be administered with pimasertib orally once daily on Days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.
其他名称：
  • MSC1936369B
药品：FOLFIRI
Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter [mg/m^2] intravenous [i.v] infusion over 90 minutes or leucovorin [dl-leucovorin] 400 mg/m^2 i.v. infusion over 90 minutes; followed by irinotecan 180 mg/m^2 given as a 90-minute infusion in 500 milliliter [mL] dextrose 5%; followed by a bolus 5-fluorouracil [FU] 400 mg/m^2 and a 46-hour infusion 5-FU 2400 mg/m^2) at conventional doses on days 1 and 15 of the same 28 day cycle.
实验性的：Part 2 or Phase 2 Randomized part: Placebo+FOLFIRI
Planned, not performed
药品：FOLFIRI
Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter [mg/m^2] intravenous [i.v] infusion over 90 minutes or leucovorin [dl-leucovorin] 400 mg/m^2 i.v. infusion over 90 minutes; followed by irinotecan 180 mg/m^2 given as a 90-minute infusion in 500 milliliter [mL] dextrose 5%; followed by a bolus 5-fluorouracil [FU] 400 mg/m^2 and a 46-hour infusion 5-FU 2400 mg/m^2) at conventional doses on days 1 and 15 of the same 28 day cycle.
药品：Placebo
Subjects will be administered with placebo orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Part 1 or Safety Run-in Part: Maximum Tolerated Dose (MTD)
大体时间：Baseline up to Day 28 (Part 1)
MTD was defined as the dose level, at which the treatment-related dose limiting toxicity (DLT) occurred in >1 of 3 subjects or in >1 of 6 subjects. DLT was defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Any Grade >=3 non-hematological toxicity except for Grade 4 asymptomatic increases in liver function tests (LFTs) reversible within 7 days in subjects with liver involvement, Grade 3 asymptomatic increases in LFTs reversible within 7 days in subjects without liver involvement, Grade 3 vomiting controlled with adequate and optimal therapy and prophylaxis, and Grade 3 diarrhea controlled with adequate and optimal anti-diarrhea therapy; any Grade 4 neutropenia lasing >5 days/ febrile neutropenia lasting >1 day; any Grade 4 thrombocytopenia/Grade 3 with bleeding; any treatment delay >2 weeks due to trial treatment-related adverse effects at any dose level and judged to be possibly or probably related to the trial treatment.
Baseline up to Day 28 (Part 1)
Part 2 or Phase 2 Randomised Part: Progression Free Survival (PFS)
大体时间：From randomization up to first documented disease progression maximum up to 2 years
PFS was defined as time (in months) from the date of randomization to the first documentation of disease progression as reported and documented by the Investigator (i.e. radiological progression per RECIST v1.0) or death for any cause.
From randomization up to first documented disease progression maximum up to 2 years

次要结果测量

结果测量
措施说明
大体时间
Part 1 or Safety Run-in Part: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
大体时间：From the first dose of study drug administration up to 28 days after the last dose of study drug administration
An AE is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
From the first dose of study drug administration up to 28 days after the last dose of study drug administration
Part 1 or Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Pimasertib, Irinotecan and SN-38
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Time to Reach Maximum Observed Concentration (Tmax) of Pimasertib, Irinotecan and SN-38
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Area Under the Concentration-time Curve From Time Zero to the Time of Last Observation (AUC0-t) of Pimasertib, Irinotecan and SN-38
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration is at or above the lower limit of quantification.
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib, Irinotecan and SN-38
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
The AUC(0-inf) of pimasertib and irinotecan was estimated by determining the total area under the concentration time curve extrapolated to infinity.
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Apparent Terminal Half Life (t1/2) of Pimasertib, Irinotecan and SN-38
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
The t1/2 was defined as the time required for the plasma concentration of pimasertib and irinotecan to decrease 50% in the final stage of elimination.
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Apparent Oral Clearance (CL/f) of Pimasertib, (CL) Irinotecan and SN-38
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Clearance of a drug was a measure of the rate at which drug was metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Apparent Oral Volume of Distribution (Vz f) Pimasertib, (Vz) of Irinotecan and SN-38
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Ratio of Cmax for Pimasertib (Day 1/Day 8), Irinotecan and SN-38 (Day 1/Day 15)
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan and SN-38
Part 1 or Safety Run-in Part: Ratio of AUC0-inf of Pimasertib (Day 1/Day 8), Irinotecan and SN-38 (Day 1/Day 15)
大体时间：Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan
The AUC(0-inf) was estimated by determining the total area under the concentration time curve extrapolated to infinity.
Day 1 and Day 8 for pimasertib; Day 1 and Day 15 for Irinotecan
Part 1 or Safety Run-in Part: Number of Subjects With Best Overall Response (BOR)
大体时间：Up to 2 years
BOR was defined based on Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST V1.0) as following: Complete response (CR) was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. Partial response (PR) was defined as at least a 30 percent (%) decrease in the sum of the longest diameters (SLD) of the targeted lesions. CR and PR had to be documented on 2 occasions separated by at least 4 weeks (28 days). Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) being demonstrated during the first 4 weeks. PD was defined as at least a 20% increase in the SLD of target lesions compared to the smallest SLD since the study treatment started.
Up to 2 years
Part 1 or Safety Run-in Part: Circulating Biomarkers in Serum
大体时间：Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
Part 2 or Phase 2 Randomized Part: Circulating Biomarkers
大体时间：Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
Predose, Day 1, 2 and 16 of cycle 1 followed by Day 1 pre-dose of every second cycle up to 2 years
Part 2 or Phase 2 Randomized Part: Best Overall Response
大体时间：Up to 2 years
BOR was defined based on Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST V1.0) as following: Complete response (CR) was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. Partial response (PR) was defined as at least a 30 percent (%) decrease in the sum of the longest diameters (SLD) of the targeted lesions. CR and PR had to be documented on 2 occasions separated by at least 4 weeks (28 days). Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) being demonstrated during the first 4 weeks. PD was defined as at least a 20% increase in the SLD of target lesions compared to the smallest SLD since the study treatment started.
Up to 2 years
Part 2 or Phase 2 Randomized Part: Number of Subjects With TEAEs, Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
大体时间：From the first dose of study drug administration up to 28 days after the last dose of study drug administration
An AE is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAES between first dose of study drug administration and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
From the first dose of study drug administration up to 28 days after the last dose of study drug administration

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

EMD Serono

调查人员

  • 研究主任：Medical Responsible、Merck Serono S.A., Geneva

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2010年3月1日

初级完成 (实际的)

2012年4月1日

研究完成 (实际的)

2012年4月1日

研究注册日期

首次提交

2010年3月4日

首先提交符合 QC 标准的

2010年3月10日

首次发布 (估计)

2010年3月11日

研究记录更新

最后更新发布 (估计)

2016年10月19日

上次提交的符合 QC 标准的更新

2016年8月24日

最后验证

2016年8月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • EMR200066_004

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

Pimasertib的临床试验

搜索类似试验

赞助者和合作者

医疗条件

药物干预

CROs by country

CROs in Canada

条件

罕见疾病

药物干预

膳食补充剂

赞助者/合作者

地点

订阅