A Randomized, Double-Blind Placebo-Controlled Phase II Study of the MEK Inhibitor GSK1120212 Plus Gemcitabine vs Placebo Plus Gemcitabine in Subjects With Metastatic Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
GSK1120212 is a potent and highly selective inhibitor of MEK phosphorylation and kinase activity and has demonstrated potent anti-proliferative activity against human pancreatic cancer cell lines. This study is a Phase II, randomized placebo-controlled trial of the MEK inhibitor GSK1120212 plus gemcitabine vs. placebo plus gemcitabine in subjects with metastatic pancreatic cancer. Eligible subjects will receive intravenous gemcitabine with oral GSK1120212 or placebo. Therapy will continue until treatment discontinuation criteria are met. The primary objective will be to compare the overall survival of subjects in the GSK1120212 plus gemcitabine arm vs. subjects in the placebo plus gemcitabine arm. Secondary objectives include comparison of progression free survival, overall response rate, and duration of response between the two arms. Exploratory research objectives include the evaluation of population pharmacokinetics as well as blood and tissue based biomarkers. Safety will also be monitored throughout dosing.
Once the determined number of survival events has occurred, if subjects are eligible, they will have the option to enter MEK114375, an open-label, Phase Ib rollover study of GSK1120212 monotherapy or GSK1120212 in combination with other anti-cancer treatments.
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
- Double (Participant, Outcomes Assessor)
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
- •18 years old or older
- •Histologically or cytologically confirmed diagnosis of metastatic (Stage IV) adenocarcinoma of the pancreas with measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale
- •All prior treatment related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.0) ≤ Grade 1 (except alopecia) at the time of randomization
- •Adequate baseline organ function
- •Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
排除标准
- •Prior systemic therapy (i.e., chemotherapy, immunotherapy, hormone therapy, , targeted therapy or any investigational anti-cancer drug) for metastatic pancreatic adenocarcinoma.
- •(Prior treatment with 5-FU based or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. Prior systemic chemotherapy in the adjuvant setting is allowed ; however, prior therapy with gemcitabine is allowed only if tumor recurrence occurred at least 6 months after completing the last dose of gemcitabine)
- •History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above
- •Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator or GSK Medical Monitor
- •History of interstitial lung disease or pneumonitis
- •History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
- •Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
- •History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 6 months
研究组 & 干预措施
GSK1120212 plus Gemcitabine
GSK1120212 administered orally plus gemcitabine IV
干预措施: GSK1120212 (Drug)
GSK1120212 plus Gemcitabine
GSK1120212 administered orally plus gemcitabine IV
干预措施: Gemcitabine (Drug)
Placebo plus Gemcitabine
Placebo administered orally plus gemcitabine IV
干预措施: Gemcitabine (Drug)
Placebo plus Gemcitabine
Placebo administered orally plus gemcitabine IV
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Survival
时间窗: From randomization until death due to any cause or until the data cutoff of 15-March-2013 (up to 24 months)
Overall survival is defined as the time from randomization until death due to any cause. For the analysis of overall survival, the last date of known contact was used for those participants who were not dead at the time of analysis; such participants were considered censored.
次要结局
- Investigator-Assessed Duration of Response(From the first documented CR or PR until disease progression or death due to any cause or until the data cutoff of 17-April-2012 (up to 13 months))
- Number of Participants With an Investigator-assessed Best Response, With or Without Confirmation, of Complete Response (CR) or Partial Response (PR)(From randomization until disease progression or death due to any cause or until the data cutoff of 17-April-2012 (up to 15 months))
- Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)(From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 15-March-2013 (up to 21 months))
- Number of Participants (Par.) With a Worst-case Change to Grade 3 or Grade 4 From Baseline Grade in Chemistry Parameters(From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 17-April-2012 (up to 17 months))
- Progression-free Survival (PFS) as Assessed by the Investigator(From randomization until disease progression (PD) or death due to any cause or until the data cutoff of 17-April-2012 (up to 15 months))
- Number of Participants With Change From Baseline Increase to Grade 3/Grade 4 in Lab Hematology Test Measurements(From the start of the first dose of study treatment until 28 days following discontinuation of the study treatment or until the data cutoff of 17-April-2012 (up to 17 months))