BMS-986205 and Nivolumab as First Line Therapy in Treating Patients With Liver Cancer

赞助:

合作者:

信息的提供 (责任方):

Edward Kim，University of California, Davis

追踪信息

首次提交日期 ^ICMJE

October 2, 2018

首次发布日期e ^ICMJE

October 4, 2018

最后更新发布日期

October 4, 2018

预计研究开始日期 ^ICMJE

December 1, 2018

预计主要完成日期

December 1, 2021 (主要结果测量的最终数据收集日期)

目前主要观察指标 ^ICMJE

Incidence of adverse events (AE)[ Time Frame: Up to 100 days ]

Safety profile will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (V)5.0 criteria. Dose-limiting toxicities (DLTs), adverse events, serious adverse events, and clinical laboratory values outside normal limits will be listed for each patient and summarized by body system and dose level in frequency tables.

Objective response rate (ORR)[ Time Frame: Up to 3 years ]

ORR is defined as the percentage of patients that achieve partial response (PR) or complete response (CR). The ORR will be estimated as the proportion of participants who experience an objective response, along with its exact 95% confidence interval.

原始主要观察测量 ^ICMJE

与当前相同

目前的二级观察 ^ICMJE

Disease control rate (DCR)[ Time Frame: Up to 3 years ]
DCR is defined as the percentage of patients that achieve an objective tumor response or have stable disease to therapy. The DCR will be estimated as the proportion of participants who experience an objective response, along with its exact 95% confidence interval.
Progression-free survival (PFS)[ Time Frame: From date of enrollment to time of progression or death, whichever occurs first, assessed up to 3 years ]
PFS will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.
Duration of response (DOR)[ Time Frame: From the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or progressive disease (PD) is objectively documented, assessed up to 3 years ]
DOR will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.
Overall survival (OS)[ Time Frame: From date of enrollment to death from any cause, assessed up to 3 years ]
OS will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.

描述性信息

简略标题 ^ICMJE

BMS-986205 and Nivolumab as First Line Therapy in Treating Patients With Liver Cancer

正式标题 ^ICMJE

Phase I/II Trial of BMS-986205 and Nivolumab as First Line Therapy in Hepatocellular Carcinoma

简要概况

This phase I/II trial studies the side effects and best dose of IDO1 inhibitor BMS-986205 (BMS-986205) when given together with nivolumab and how well it works as first line therapy in treating patients with liver cancer. BMS-986205 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving BMS-986205 and nivolumab may work better in treating patients with liver cancer.

详细说明

PRIMARY OBJECTIVES: I. To obtain the safety and tolerability of BMS-986205 in combination with nivolumab in unresectable / metastatic hepatocellular carcinoma (HCC) in the first line setting using Common Terminology Criteria for Adverse Events (CTCAE) version (V)5.0 criteria. II. To determine efficacy as defined by objective response rate (ORR) of BMS-986205 in combination with nivolumab in unresectable / metastatic HCC in the first line setting using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1). SECONDARY OBJECTIVES: I. To determine disease control rate (DCR), duration of response (DOR), progression free survival (PFS), and overall survival (OS) by RECIST 1.1 and ORR using immune RECIST (iRECIST) of BMS-986205 in combination with nivolumab in unresectable HCC. (Phase II) II. To further evaluate safety of BMS-986205 in combination with nivolumab in unresectable HCC. (Phase II) OUTLINE: This is a phase I, dose-escalation study of IDO1 inhibitor BMS-986205 followed by a phase II study. Patients receive IDO1 inhibitor BMS-986205 orally (PO) once daily (QD) on days 1-14 and nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 100 days, and then every 3 months thereafter.

研究类型 ^ICMJE

Interventional

研究阶段

Phase 1/Phase 2

研究设计 ^ICMJE

分配:
干预模型: Single Group Assignment
干预模型描述:
盲法: Interventional
盲法描述:
主要目的: Treatment

适用条件 ^ICMJE

干预项目 ^ICMJE

Drug: IDO1 Inhibitor BMS-986205
Given PO
Biological: Nivolumab
Given IV

研究工具

Experimental: Treatment (BMS-986205 and nivolumab)
Patients receive IDO1 inhibitor BMS-986205 PO QD on days 1-14 and nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

招募信息

招募状态 ^ICMJE

Not yet recruiting

预计入组 ^ICMJE

原始预计入组 ^ICMJE

与当前相同

预计研究完成日期

June 1, 2022

预计主要完成日期

December 1, 2021 (主要结果测量的最终数据收集日期)

合格标准 ^ICMJE

Inclusion Criteria: - Willing and able to provide written informed consent for the trial - Life expectancy > 12 weeks - Histologically or imaging confirmed hepatocellular carcinoma (mixed hepatocellular/cholangiocarcinoma or fibrolamellar subtypes are excluded) - Have disease that is not amenable for curative treatment approach - Have measurable disease based on RECIST v1.1 - >= 1 liver lesions accessible for core biopsy that was either not previously treated by liver-directed therapy or progressed following liver-directed therapy - Child-Pugh score of A - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Absolute neutrophil count (ANC) >= 1000 cell/mm^3 - Platelet count >= 50,000/mm^3 - Hemoglobin (Hgb) >= 8 g/dL - Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 5 x upper limit of normal (ULN) - Total bilirubin =< 2 ULN - Creatinine =< 2 x ULN - Subjects with active hepatitis B virus (hep B) are allowed if antiviral therapy for hepatitis B has been given for > 8 weeks and viral load is < 100 IU/ml prior to first dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed - Willingness to undergo mandatory pre-treatment biopsy (unless there is adequate archival tumor specimen available) and mandatory on-treatment biopsy - Female subject of child-bearing potential must have a negative urine pregnancy =< 24 hour (hr) prior to planned treatment initiation. Women with childbearing potential and males must be willing to use adequate birth control on trial and until 5 months for women or 7 months for men after the last of study therapy - Ability to adhere to the study visit schedule and other protocol requirements - Participants must be able to swallow pills intact Exclusion Criteria: - Received prior systemic HCC-related therapy or currently receiving HCC-related systemic treatment or participating in a clinical trial and receiving study therapy - Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) - Known diagnosis of immunodeficiency or active autoimmune disease or requiring systemic steroid equivalent of prednisone >= 10 mg/day or any immunosuppressive therapies =< 7 days of before the first dose of the study - Active bacterial, viral (except hepatitis B and C), or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, anti-viral therapy, anti-fungal therapy, and/or other treatment - Known history of pneumonitis (non-infectious) or evidence of interstitial lung disease - Clinically significant ascites - Hepatic encephalopathy - Any significant medical condition including additional malignancies, laboratory abnormalities, or psychiatric illness that would prevent the subject from participating and adhering to study related procedures - Live attenuated vaccine =< 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed - Use of strong inhibitor / inducer of CYP3A4 or CYP1A2 - Known history of surgery or medical condition that may affect drug absorption - Participants with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD deficiency prior to randomization using quantitative or qualitative G6PD assay results to suggest underlying G6PD deficiency - Participants with a personal or family (i.e., in a first-degree relative) history or presence of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases that puts them at risk of methemoglobinemia. All participants will be screened for methemoglobin levels prior to enrollment using blood methemoglobin > ULN, assessed in an arterial or venous blood sample or by co oximetry - Subjects with screening corrected QT (QTc) interval > 480 ms - Liver directed therapy =< 4 weeks before the first dose of study - History of esophageal or gastric variceal bleeding within 3 months of study enrollment - Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization - Prior history of serotonin syndrome

性别

参与研究的性别:

All

年龄

最小年龄：18 Years ，最大年龄：N/A

接受健康的志愿者

没有

可入组国家 ^ICMJE

United States

管理信息

数据检测委员会

Yes

研究涉及美国FDA监管的产品

研究美国FDA监管的药品: Yes
研究涉及美国FDA监管的设备产品: No

IPD 共享声明

计划分享 IPD:

责任方

Edward Kim，University of California, Davis

研究赞助商 ^ICMJE

Edward Kim

合作者 ^ICMJE

研究员 ^ICMJE

Principal Investigator: Edward Kim University of California, Davis

PRS 账户

University of California, Davis

验证日期

October 2018

^ICMJE 国际医学期刊编辑委员会和世界卫生组织 ICTRP 要求的元素

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