A Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors
2020年10月30日 更新者：Effector Therapeutics
A Phase 1-2 Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of daily oral administration of eFT508.
研究概览
详细说明
eFT508 is an oral, potent and highly selective inhibitor of mitogen-activated protein kinase interacting kinase (MNK) 1 and 2. Dysregulated translation of messenger RNA (mRNA) plays a role in the pathogenesis of multiple solid tumors and hematological malignancies.
MNK1 and MNK2 integrate signals from several oncogenic and immune signaling pathways (including RAS, p38 and Toll-like receptors) by phosphorylating eukaryotic initiation of factor 4E (eIF4E) and key effector proteins.
Phosphorylation of these regulatory proteins by MNK1 and MNK2 selectively regulates the stability and translation of a subset of cellular mRNA that control tumor growth, the tumor microenvironment and immune signaling.
Nonclinical studies indicate that eFT508 shows activity against various types of solid tumors.
These nonclinical studies support initiation of clinical development of eFT508 in patients with cancer.
研究类型
介入性
注册 (实际的)
66
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
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Colorado
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Denver、Colorado、美国、80218
- SCRI at HealthOne
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Florida
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Sarasota、Florida、美国、34232
- Florida Cancer Specialists
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Tennessee
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Nashville、Tennessee、美国、37203
- Tennessee Oncology, PLLC
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Texas
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Houston、Texas、美国、77030
- MD Anderson Cancer Center
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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:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Pathologically documented diagnosis of advanced solid tumor malignancy that progressed after appropriate prior therapy or has no potential for cure with currently available treatments.
- Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) outside of any prior radiation field.
- At least 3 weeks post any treatments/therapies at the time of first dose.
- Adequate bone marrow function.
- Adequate hepatic function.
- Adequate renal function.
- Normal coagulation panel.
- Negative antiviral serology.
- Willingness to use effective contraception.
Exclusion Criteria:
- Known central nervous system malignancy.
- Gastrointestinal disease that may interfere with drug absorption.
- Significant cardiovascular disease.
- Significant ECG abnormalities.
- Ongoing risk of bleeding due to active peptic ulcer disease, bleeding diathesis, or requirement for systemic anticoagulants. Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.
- Ongoing systemic bacterial, fungal or viral infection (with the exception of fungal infections of the skin or nails).
- Pregnancy or breastfeeding.
- Major surgery within 4 weeks before the start of study therapy.
- Prior solid organ or bone marrow progenitor cell transplantation.
- Prior therapy with any known inhibitor of MNK1 or MNK2.
- Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids (can be using topical or inhaled corticosteroids).
- Use of drugs that might pose a risk of a drug-drug interaction within 4-7 days before the start of study therapy.
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：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：eFT508
Escalation cohort
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Will be given orally once or twice daily.
Each treatment cycle = 21 days.
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Maximum tolerated dose (MTD)/Recommended dose (RD)
大体时间：Up to one year
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Up to one year
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Overall response rate (ORR)
大体时间：Up to three years
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Up to three years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Safety (Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03))
大体时间：Up to three year
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Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03)
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Up to three year
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Plasma concentration of eFT508 as characterized by maximum serum concentration (Cmax)
大体时间：Different time points up to 336 hours
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Different time points up to 336 hours
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Plasma concentration of eFT508 as characterized by Area Under the Curve (AUC)
大体时间：Different time points up to 336 hours
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Different time points up to 336 hours
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Changes in eIF4E phosphorylation in peripheral blood cells (PBMCs)
大体时间：Up to Day 14
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Up to Day 14
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Tumor control evaluated by modified RECIST criteria v 1.1
大体时间：Up to three years
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Up to three years
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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。
调查人员
- 研究主任：Jeremy Barton, MD、Effector Therapeutics
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 (实际的)
2015年12月3日
初级完成 (实际的)
2019年1月11日
研究完成 (实际的)
2019年3月22日
研究注册日期
首次提交
2015年11月9日
首先提交符合 QC 标准的
2015年11月12日
首次发布 (估计)
2015年11月16日
研究记录更新
最后更新发布 (实际的)
2020年11月2日
上次提交的符合 QC 标准的更新
2020年10月30日
最后验证
2020年10月1日
更多信息
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.
eFT508的临床试验
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Effector TherapeuticsPfizer; Merck KGaA, Darmstadt, Germany完全的
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Effector Therapeutics终止
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Translational Research in OncologyStand Up To Cancer; Effector Therapeutics完全的
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Effector TherapeuticsMedpace, Inc.; ICON plc主动，不招人
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Northwestern UniversityNational Cancer Institute (NCI); EFFECTOR Therapeutics, Inc.主动，不招人