A Safety and Efficacy Study of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellular Carcinoma (HCC)
A Phase 1/2, MultiCenter, Open-label, Dose Finding Study to Assess the Safety, Tolerability and Preliminary Efficacy of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellullar Carcinoma (HCC) Following First Line Treatment Failure
研究概览
详细说明
Study population included subjects who had progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.
The dose escalation part of the study was designed to explore three dose levels of CC-122 to identify the recommended phase 2 dose (RP2D) to be used in the expansion phase. Approximately 20 subjects were to be enrolled in the dose escalation part of the study. Subjects could be treated for up to 2 years, or until progression of disease, unacceptable toxicity, subject/physician decision, withdrawal of consent, death. Safety follow up until 28 days after CC122 treatment and 90 days after nivolumab treatment. RECIST 1.1 criteria was used to determine response. Survival follow up until death, withdrawal of consent, or the study closes. Subjects were permitted to continue treatment beyond progression (TBP) if they continue to meet protocol criteria, had stable performance status, had clinical benefit, other treatment options were discussed. A separate ICF was signed to continue TBP.
During the dose escalation phase, CC-122 was administered orally 5 consecutive days out of 7 (5 days on/2 days off weekly) on Days 1 to 5, 8 to 12, 15 to 19 and 22 to 26 of each 28-day cycle. Once the RP2D for dosing of CC-122 in combination with nivolumab was defined, expansion (Phase 2) would start. A modified 3+3 dose escalation design was used to identify the initial toxicity of the combination. Up to six subjects were concurrently enrolled into a dose level. Decisions as to which dose level to enroll a new subject were based on the number of subjects enrolled and evaluable, the number of subjects experiencing DLTs, and the number of subjects enrolled but who are not yet evaluable for toxicity in the current cohort at the time of new subject entry. A Safety Review Committee (SRC) comprised of investigators participating in the study made dose escalation decisions based on these criteria.
After completion of the Dose Escalation Phase, the Dose Expansion Phase of the study did not proceed due to the changing landscape in the treatment of HCC. There were no additional safety concerns or safety signals identified in the dose escalation phase of the study.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Milan、意大利、20089
- IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
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Pavia、意大利、27100
- Fondazione IRCCS Policlinico San Matteo
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Roma、意大利、144
- Istituto Nazionale Tumori Regina Elena
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Marseille Cedex 9、法国、13273
- Institut Paoli Calmettes
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Rennes、法国、35200
- Centre Eugene Marquis
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Toulouse Cedex、法国、31059
- Institut Universitaire du Cancer IUCT - Oncopole
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Villejuif CEDEX、法国、94805
- Institut Gustave Roussy Hematologie
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California
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Los Angeles、California、美国、90095-1752
- UCLA Division of Hematology Oncology
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Florida
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Gainesville、Florida、美国、32610
- University of Florida
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New York
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New York、New York、美国、10016
- NYU Langone Medical Center
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Texas
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Dallas、Texas、美国、75251
- Mary Crowley Cancer Research
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Barcelona、西班牙、8035
- Hospital Universitario Vall D Hebron
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Madrid、西班牙、28034
- Hospital Ramón y Cajal
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Madrid、西班牙、28041
- Hospital 12 de Octubre
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Subjects must satisfy the following criteria to be enrolled in the study:
- Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
- Subject has a confirmed pathologic diagnosis of Hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) Guidelines.
- Subjects who have progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.
- Subject has at least one measurable lesion according to RECIST 1.1.
- Subject has a life expectancy of ≥ 12 weeks
- Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Subject has adequate hematologic function and adequate hepatic function at screening
Exclusion Criteria:
- The presence of any of the following will exclude a subject from enrollment:
- Subject has received more than 2 previous systemic therapies for Hepatocellular carcinoma (HCC).
- Subject has received previous treatment with any anti-PD-1 (Programmed death 1) or anti-PD-L1 (PD-1 ligand receptor) antibody
学习计划
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:CC-122 with Nivolumab
CC-122 orally 5/7 days with nivolumab Intravenously (IV) 3mg/kg every 2 weeks.
Cohorts of up to 6 subjects per dose level until Recommended Phase 2 dose (RP2D).
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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 |
---|---|---|
Incidence of Dose Limiting Toxicities (DLTs)
大体时间:28 days
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During dose escalation, the DLT assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2. A DLT is defined as any of the following toxicities occurring within the DLT assessment window unless the event can clearly be determined to be unrelated to the drug. |
28 days
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Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
大体时间:From first dose up to 28 days (CC-122) or 90 days (nivolumab) post-last dose (up to 2 years)
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During dose escalation, the TEAE phase 1 assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2. Number of participants who experienced a TEAE during the course of the study. |
From first dose up to 28 days (CC-122) or 90 days (nivolumab) post-last dose (up to 2 years)
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Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
大体时间:up to 2 years
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ORR is is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR).
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up to 2 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Disease Control Rate (DCR) by RECIST 1.1
大体时间:up to 2 years
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DCR is is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) or stable disease (SD).
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up to 2 years
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Duration of Response (DoR) by RECIST 1.1
大体时间:up to 2 years
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Duration of response is measured from the date the criterion is first met for CR/PR using RECIST 1.1 rules (whichever is first recorded) until the first date when progressive disease using RECIST 1.1 is documented or death occurred.
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up to 2 years
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Progression-Free Survival (PFS) by RECIST 1.1
大体时间:up to 2 years
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Progression-Free Survival (PFS) is defined as the time from the first dose date of study drug until tumor progression or death, whichever occurs first. A subject who has neither progressed nor died or who progresses or dies after an extended lost-to-follow up time (two or more missed assessments) is censored on the date of last adequate tumor assessment. Subjects without valid baseline or post-baseline tumor assessments are censored on their first dose date. Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data. |
up to 2 years
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Overall Survival (OS) by RECIST 1.1
大体时间:up to 2 years
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Overall Survival (OS) is measured as the time from the first dose of study drug to death from any cause. Participants who have no death reported are censored at the last contact date the participant is known to be alive. Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data. |
up to 2 years
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Time to Progression (TTP) by RECIST 1.1
大体时间:up to 2 years
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Time to Progression (TTP) is defined as the time from the first dose date of study drug until tumor progression; TTP does not include death. The censoring rules are the same as PFS except that deaths without progression are censored at last adequate tumor assessment. Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data. |
up to 2 years
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Maximum Observed Concentration (Cmax)
大体时间:28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Area Under the Concentration Time Curve (AUC)
大体时间:28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Time to Maximum Concentration (Tmax)
大体时间:28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Terminal Half-life (T-HALF)
大体时间:28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Apparent Volume of Distribution (Vz/F)
大体时间:28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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合作者和调查者
赞助
调查人员
- 研究主任:Akshay Patel、Celgene Corporation
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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