Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)
2019年2月25日 更新者:Merck Sharp & Dohme LLC
A Phase Ib/II Study to Evaluate the Safety and Tolerability of Preladenant as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Malignancies
The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy.
This study will be done in 2 parts.
Part 1 will identify and confirm the recommended Phase 2 dose (RP2D) of preladenant when given alone or in combination with pembrolizumab.
Part 2 of the study will determine the safety and efficacy of preladenant in combination with pembrolizumab at the RP2D in participants with select solid tumors .
研究概览
研究类型
介入性
注册 (实际的)
10
阶段
- 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
-
-
-
Haifa、以色列
- Rambam Health Care Campus ( Site 0020)
-
Tel Aviv、以色列
- Tel Aviv Sourasky Medical Center ( Site 0021)
-
-
-
-
Ontario
-
Toronto、Ontario、加拿大、H9H 4M7
- Princess Margaret Hospital ( Site 0010)
-
-
Quebec
-
Montreal、Quebec、加拿大、H9H 4M7
- Jewish General Hospital ( Site 0011)
-
-
-
-
Michigan
-
Grand Rapids、Michigan、美国、49546
- START Midwest ( Site 0001)
-
-
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:
- Has a histologically- or pathologically-documented, locally-advanced or metastatic solid tumor for which standard therapy, either does not exist or has been proven ineffective, intolerable or refused by the participant. Each participant must have received at least one and up to five prior lines of cancer treatment regimens, excluding neo-adjuvant, adjuvant, maintenance treatment and surgery
- Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)
- Has measurable disease per RECIST 1.1
- Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Females must not be pregnant
- Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study therapy, throughout the study period, and for up to 120 days after the last dose of study therapy
Exclusion Criteria:
- Has disease that is suitable for local treatment administered with curative intent
- Has received previous treatment with an immunomodulatory agent (e.g, anti- Programmed Cell Death Receptor 1/ Programmed Cell Death Receptor Ligand 1 or anti-cytotoxic T-lymphocyte-associated antigen-4) and was discontinued from treatment due to a Grade 3 or higher immune-related adverse event
- Has received previous treatment with an adenosine A2a receptor antagonist (e.g. CPI-444, HTL1071, PBF-509)
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks of the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse event
- Is currently participating or has participated in a study with an investigational agent or using an investigational device within 28 days of the first dose of study therapy
- Is currently taking or has taken drugs that interfere with Cytochrome P450 (CYP)3A4 or CYP2C8 or grapefruit and star fruit in diet within 14 days of the first dose of study therapy
- Is currently taking or has taken proton pump inhibitors within 5 days of the first dose of study therapy
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of the first dose of study therapy
- Is expected to require any other form of systemic or localized antineoplastic therapy while on study
- Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years
- Has clinically active central nervous system metastases and/or carcinomatous meningitis
- History of a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study drug
- Has an active infection requiring therapy
- History of interstitial lung disease
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- History of active tuberculosis
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has received a live-virus vaccine within 30 days of the first dose of study therapy
- Has known Human Immunodeficiency Virus (HIV) (HIV 1 or 2 antibodies) and/or known active and acute Hepatitis B or C infections
- Has known psychiatric or substance abuse disorders that would interfere with the ability to cooperate with the requirements of the study
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
- Has not fully recovered from any effects of major surgery without significant detectable infection
- Has had surgery that required general anesthesia within 2 weeks of the first dose of study therapy
- Has had surgery that required regional/epidural anesthesia within 72 hours of the first dose 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:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:Preladenant 25 mg Twice a Day (BID)
During an initial dose evaluation phase, participants received 25 mg of preladenant orally twice a day (BID) on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established.
The RP2D was to be established based on the number of dose limiting toxicities (DLTs) at each dose level administered.
Participants continued receiving 25 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
|
Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
其他名称:
|
|
实验性的:Preladenant 50 mg BID
During an initial dose evaluation phase, participants received 50 mg of preladenant orally BID on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established.
The RP2D was established based on the number of DLTs at each dose level administered.
Participants continued receiving 50 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
|
Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
其他名称:
|
|
实验性的:Preladenant + Pembrolizumab
During an initial dose evaluation phase, participants received 25 mg of preladenant administered orally BID on Days 1 through 21 in combination with 200 mg pembrolizumab administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (for a maximum of 35 cycles).
Participants continued receiving preladenant 25 mg BID in combination with 200 mg pembrolizumab for each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
|
Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
其他名称:
Administered as IV infusion on Day 1 of each 21-day cycle
其他名称:
|
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 |
|---|---|---|
|
Number of Participants With Dose-limiting Toxicities (DLTs)
大体时间:Cycle 1 (up to 21 days)
|
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for >72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN) WITH total bilirubin >2X ULN with no elevation in alkaline phosphatase (<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a >2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing >25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.
|
Cycle 1 (up to 21 days)
|
|
Number of Participants Who Experienced at Least One Adverse Event (AE)
大体时间:Up tp approximately 8 months
|
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment.
An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure.
Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
The number of participants who experienced at least one AE is presented.
|
Up tp approximately 8 months
|
|
Number of Participants Who Discontinued Study Treatment Due to an AE
大体时间:Up to approximately 8 months
|
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment.
An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure.
Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
The number of participants who discontinued study treatment due to an AE is presented.
|
Up to approximately 8 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
大体时间:Up to approximately 8 months
|
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 per investigator review.
The ORR per RECIST 1.1 for participants is presented.
|
Up to approximately 8 months
|
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。
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)
2017年6月27日
初级完成 (实际的)
2017年11月24日
研究完成 (实际的)
2018年2月21日
研究注册日期
首次提交
2017年3月30日
首先提交符合 QC 标准的
2017年3月30日
首次发布 (实际的)
2017年4月4日
研究记录更新
最后更新发布 (实际的)
2019年6月5日
上次提交的符合 QC 标准的更新
2019年2月25日
最后验证
2019年2月1日
更多信息
与本研究相关的术语
其他研究编号
- 3814A-062
- MK-3814A-062 (其他标识符:Merck Protocol Number)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
是的
IPD 计划说明
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
药物和器械信息、研究文件
研究美国 FDA 监管的药品
是的
研究美国 FDA 监管的设备产品
不
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.