Dose Escalation Study of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies
2019年6月28日 更新者：Millennium Pharmaceuticals, Inc.
A Phase I, Open Label, Dose Escalation Study of Oral Administration of MLN0128 in Combination With Paclitaxel, With/Without Trastuzumab, in Subjects With Advanced Solid Malignancies
This is a Phase I, open label, dose escalation study of oral administration of MLN0128 in combination with paclitaxel, with/without trastuzumab, in participants with advanced solid malignancies.
研究概览
详细说明
This is a Phase I, open-label study consisting of a dose escalation phase in advanced solid malignancies to determine the maximum tolerated dose (MTD) of oral administration of MLN0128 in 1 or more dosing schedules, combined with paclitaxel on Days 1, 8 and 15 of each cycle, followed by an expansion phase for further safety and preliminary efficacy.
Once the MTD is determined for each of the dosing schedules evaluated, a dose and schedule will be selected for the expansion phase, which may enroll participants into 2 arms in parallel:
- Arm A will consist of HER2- unknown cancer participants receiving MLN0128+paclitaxel
- Arm B will consist of HER2+ cancer participants receiving MLN0128+paclitaxel plus weekly trastuzumab
研究类型
介入性
注册 (实际的)
68
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
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Florida
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Fort Myers、Florida、美国、33905
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Oklahoma
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Oklahoma City、Oklahoma、美国、73104
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Tennessee
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Nashville、Tennessee、美国、37203
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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:
- Voluntary written consent
- Locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Ability to swallow oral medications
- For women of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to the first study drug administration and use of physician-approved method of birth control from 30 days prior to 30 days following the last study drug administration
- Male participants must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration
- Clinical laboratory values as specified in the protocol
- For expansion phase (Arm A) - HER2-/unknown participants will be enrolled
- For expansion phase (Arm B) - HER2+ cancer participants will be enrolled
Exclusion Criteria:
- Diagnosis of primary brain tumor
- Have received prior cancer or other investigational therapy within 2 weeks prior to the first administration of study drug
- Known impaired cardiac function or clinically significant cardiac disease
- Known treatment with systemic corticosteroid within one week prior to the first administration of study drug
- Diabetes mellitus
- Human immunodeficiency virus (HIV) infection
- Known active cardiovascular disease condition as specified in protocol
- Pregnancy (positive serum or urine pregnancy test) or breast feeding
- Malabsorption due to prior gastrointestinal (GI) surgery, GI disease
- Other clinically significant co-morbidities
Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons
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 |
|---|---|
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实验性的：MLN0128P 30 mg QW
MLN0128 and paclitaxel (MLN0128P): MLN0128 30 mg, capsule, orally, once weekly (QW) + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128P 40 mg QW
MLN0128 40 mg, capsule, orally, once a week (QW) + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128P 6 mg QD×3d QW
MLN0128 6 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128P 7 mg QD×3d QW
MLN0128 7 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128P 8 mg QD×3d QW
MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128P 9 mg QD×3d QW
MLN0128 9 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128P 10 mg QD×3d QW
MLN0128 10 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128P 7 mg QD×5d QW
MLN0128 7 mg, capsule, orally, once daily 5 days on/2 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
|
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实验性的：MLN0128P 8 mg QD×3d QW HER2-
MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in human epidermal growth factor receptor 2 negative (HER-) cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
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实验性的：MLN0128PH 8 mg QD×3d QW HER2+
MLN0128 + paclitaxel + trastuzumab (MLN0128PH): MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m^2, 1 hour infusion, on Days 1, 8 and 15 plus trastuzumab 4 mg/kg loading dose on Day 1 followed by 2 mg/kg, intravenous each week of a 4-week cycle in HER+ cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase.
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MLN0128 capsules
paclitaxel intravenous infusion
trastuzumab intravenous infusion
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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 |
|---|---|---|
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Dose Escalation Phase: Maximum Tolerated Dose (MTD)
大体时间：Cycle 1: Days 1 to 28
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MTD is the highest dose level at which the participants tolerate treatment without dose-limiting toxicities during the first cycle (28 days) of therapy.
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Cycle 1: Days 1 to 28
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Dose Escalation Phase: Number of Participants With at Least 1 Dose Limiting Toxicity (DLT)
大体时间：Cycle 1: Days 1 to 28
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DLT was defined as any of the following occurring during Cycle 1 (Days 1-28) and attributable to MLN0128P: Grade ≥ 3 nonhematologic toxicity; Grade 3 thrombocytopenia with hemorrhage; Grade 4 neutropenia lasting > 7 days in the absence of growth factor support; Grade 4 neutropenia of any duration associated with fever 38.5 degrees C and/or infection; Any other Grade 4 hematologic toxicity; Inability to administer at least 75 % of doses of MLN0128 within Cycle 1 due to drug-related toxicity; Any clinically significant occurrence which the investigators and sponsor agree would place participants at undue safety risk; Participants who experienced an adverse event (AE) that met the definition for a DLT.
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Cycle 1: Days 1 to 28
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Objective Response Rate (ORR)
大体时间：At screening and thereafter every 2 cycles of treatment until disease progression (Up to 65.8 weeks)
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ORR was defined as the percentage of participants with Complete Response (CR) and Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
Each cycle was a 28 day cycle.
CR was defined as the disappearance of all target lesions and for non-target lesions, the disappearance of all non-target lesions and normalization of tumor marker level.
PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions.
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At screening and thereafter every 2 cycles of treatment until disease progression (Up to 65.8 weeks)
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Percentage of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events(SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug
大体时间：First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 91.4 weeks)
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An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
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First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 91.4 weeks)
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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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Cmax: Maximum Observed Plasma Concentration for MLN0128
大体时间：Cycles 1 and 2: Day 1 or 2
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Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
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Cmin: Minimum Observed Plasma Concentration for MLN0128
大体时间：Cycles 1 and 2: Day 1 or 2
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Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0128
大体时间：Cycles 1 and 2: Day 1 or 2
|
Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i.e., C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
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Terminal Phase Elimination Half-life (T1/2) for MLN0128
大体时间：Cycle 1 Day 1
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Cycle 1 Day 1
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AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN0128
大体时间：Cycle 1 Day 1
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Cycle 1 Day 1
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AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for MLN0128
大体时间：Cycles 1 and 2: Day 1 or 2
|
Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 30 and 40 mg QW arms.
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Cycles 1 and 2: Day 1 or 2
|
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Cmax: Maximum Observed Plasma Concentration for Paclitaxel
大体时间：Cycles 1 and 2: Day 1
|
Cycles 1 and 2: Day 1
|
|
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Cmin: Minimum Observed Plasma Concentration for Paclitaxel
大体时间：Cycles 1 and 2: Day 1 or 2
|
Participants in the 6 mg QD×3d QW and 9 mg QD×3d QW were dosed with MLN0128 in conjunction with paclitaxel during Cycle 1 and Cycle 2 when PK was collected.
Participants in the 7 mg QD×3d QW cohorts were dosed with paclitaxel during Cycle 1, but were subsequently switched to MLN0128 being dosed 24 hours after paclitaxel infusion Cycle 2 (i e, C2D2).
In all the other dosing cohorts, MLN0128 was dosed 24 hours after paclitaxel infusion.
Cycle 1: Data was collected at Day 1 for the 6, 7 and 9 mg QD×3d QW arms and at Day 2 for the 8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
Cycle 2: Data was collected at Day 1 for the 6 and 9 mg QD×3d QW arms and at Day 2 for the 7,8 and 10 mg QD×3d QW, 7 mg QD×5d QW, 30 and 40 mg QW arms.
|
Cycles 1 and 2: Day 1 or 2
|
|
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Paclitaxel
大体时间：Cycles 1 and 2: Day 1
|
Cycles 1 and 2: Day 1
|
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Terminal Phase Elimination Half-life (T1/2) for Paclitaxel
大体时间：Cycle 1 Day 1
|
Cycle 1 Day 1
|
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AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Paclitaxel
大体时间：Cycle 1 Day 1
|
Cycle 1 Day 1
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AUC(0-6): Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours for Paclitaxel
大体时间：Cycle 1 Day 1
|
Cycle 1 Day 1
|
|
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AUC(0-24): Area Under the Plasma Concentration-time Curve Extrapolated to 24 Hours for Paclitaxel
大体时间：Cycle 1 Day 1
|
Cycle 1 Day 1
|
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CL: Total Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel
大体时间：Cycle 1 Day 1
|
Cycle 1 Day 1
|
|
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Vss: Volume of Distribution at Steady State Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel
大体时间：Cycle 1 Day 1
|
Cycle 1 Day 1
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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。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
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)
2011年2月28日
初级完成 (实际的)
2017年9月15日
研究完成 (实际的)
2017年9月15日
研究注册日期
首次提交
2011年2月21日
首先提交符合 QC 标准的
2011年5月9日
首次发布 (估计)
2011年5月10日
研究记录更新
最后更新发布 (实际的)
2019年8月8日
上次提交的符合 QC 标准的更新
2019年6月28日
最后验证
2019年6月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- INK128-003
- U1111-1181-8192 (其他标识符：WHO)
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
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach
for details).
To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias.
Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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.