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A Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573 in Subjects With Advanced Solid Tumors

2018年10月31日 更新者：MedImmune LLC

A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573, a Fully Human Monoclonal Antibody Directed Against Insulin-like Growth Factors I and II, in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists

Evaluate the safety and tolerability of MEDI-573 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

43

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

  • 美国
    • Arizona
      • Scottsdale、Arizona、美国、85259
        • Research Site
    • Florida
      • Jacksonville、Florida、美国、32224
        • Research Site
    • Massachusetts
      • Boston、Massachusetts、美国、02115
        • Research Site
    • Michigan
      • Detroit、Michigan、美国、48201
        • Research Site
    • Minnesota
      • Rochester、Minnesota、美国、55905
        • Research Site
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19111
        • Research Site

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 至 99年 (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:

  • Histologically confirmed advanced solid tumor for which no curative or standard therapies exist.
  • Karnofsky Performance Status ≥60.
  • Adequate hematological function.
  • Adequate organ function.
  • Women of non-child-bearing potential (defined as being >1 year post-menopausal) or using effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the investigational product may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, or total abstinence, from the time the informed consent is signed through 30 days after the last dose of MEDI-573. Male subjects with partners of child-bearing potential must be surgically sterile or use contraceptive method as described above from the time of the initiation of MEDI-573 through 30 days after the last dose of MEDI-573.

Exclusion Criteria:

  • No prior treatment within 4 weeks of study drug administration.
  • No concurrent therapy for treatment of cancer.
  • No uncontrolled diabetes.
  • New York Heart Association Grade ≥ 2 congestive heart failure.
  • History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to study entry.
  • Documented brain metastasis.
  • Pregnancy or lactation or plans to become pregnant while on study.
  • Clinically significant abnormality on ECG.

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
实验性的：MEDI-573 0.5 mg/Kg QWk Dose Escalation
Participants received MEDI-573 0.5 milligram per kilogram (mg/kg) as a 60-minute intravenous (IV) infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 1.5 mg/Kg QWk Dose Escalation
Participants received MEDI-573 1.5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 5 mg/Kg QWk Dose Escalation
Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 10 mg/Kg QWk Dose Escalation
Participants received MEDI-573 10 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 15 mg/Kg QWk Dose Escalation
Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 30 mg/Kg Q3Wk Dose Escalation
Participants received MEDI-573 30 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 45 mg/Kg Q3Wk Dose Escalation
Participants received MEDI-573 45 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 5 mg/Kg QWk Dose Expansion
Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
实验性的：MEDI-573 15 mg/Kg QWk Dose Expansion
Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
药品：MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.

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 Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
大体时间：From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573. A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
大体时间：From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs
大体时间：From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Maximum Tolerated Dose (MTD) of MEDI-573
大体时间：Cycle 1 Day 1 through Cycle 1 Day 21
The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT). The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator. 2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD.
Cycle 1 Day 1 through Cycle 1 Day 21
Number of Participants With Dose-Limiting Toxicities (DLTs)
大体时间：Cycle 1 Day 1 through Cycle 1 Day 21
A DLT was defined as any grade greater than or equal to (>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (<) 4 serum-high glucose (fasting) with duration of < 24 hours; Grade 3 fever (in the absence of neutropenia) defined as > 40.0 degree centigrade (°C) [greater than (>) 104.0°F] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade >= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period.
Cycle 1 Day 1 through Cycle 1 Day 21
Optimal Biologically Effective Dose (OBED) of MEDI-573
大体时间：From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

次要结果测量

结果测量
措施说明
大体时间
Maximum Observed Serum Concentration (Cmax) After the First Dose
大体时间：For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
The Cmax was the maximum observed serum concentration of MEDI-573.
For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Time to Reach Maximum Observed Concentration (Tmax) After the First Dose
大体时间：For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
The tmax was defined as actual sampling time to reach the maximum observed serum concentration of MEDI-573.
For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Trough Serum Concentration (Ctrough) After the First Dose
大体时间：For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
The Ctrough was the lowest serum concentration of MEDI-573 within a dosing interval.
For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Dose Normalized Cmax (Cmax/Dose) After the First Dose
大体时间：For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
The Cmax/dose was the dose-normalized maximum serum concentration of MEDI-573.
For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ)
大体时间：For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Area under the serum concentration-time curve over the first dosing interval.
For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose)
大体时间：For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
The AUCtau/dose was a measure of dose-normalized area under the serum concentration-time curve over the first dosing interval.
For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573
大体时间：Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
Two methods were used to assess the immunogenicity data: an ECL-based method and measurement of neutralizing ADA. The titer was calculated by multiplying the minimum assay dilution factor by the reciprocal of the highest dilution factor which yielded an ECL multiple equal to or greater than the screening assay cut-point factor.
Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
Objective Response Rate (ORR)
大体时间：From study entry through the end of the study, up to 3.5 years
The ORR was defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) according to the RECIST criteria The CR was defined as disappearance of all target and nontarget lesions and no new lesions; and PR was definded as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline [screening]) and no new lesions.
From study entry through the end of the study, up to 3.5 years
Progression-free Survival (PFS)
大体时间：From study entry through the end of the study, up to 3.5 years
Progression-free survival (PFS) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression or death due to any cause, whichever occurred first.
From study entry through the end of the study, up to 3.5 years
Time to Progression
大体时间：From study entry through the end of the study, up to 3.5 years
Time to disease progression (TTP) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression.
From study entry through the end of the study, up to 3.5 years
Overall Survival
大体时间：From study entry through the end of the study, up to 3.5 years
Overall survival (OS) was defined as the time from the start of treatment with MEDI-573 until death.
From study entry through the end of the study, up to 3.5 years
Time to Response (TTR)
大体时间：From study entry through the end of the study, up to 3.5 years
Time to response was defined as the duration from the start of treatment with MEDI-573 to the first documentation of objective response (confirmed CR or PR) and was only assessed in participants who had achieved objective response.
From study entry through the end of the study, up to 3.5 years
Duration of Response
大体时间：From study entry through the end of the study, up to 3.5 years
Duration of response was defined as the duration from the first documentation of objective response (confirmed CR or PR) to the first documented disease progression.
From study entry through the end of the study, up to 3.5 years
Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573
大体时间：From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
The suppression profiles of both IGF-1 and IGF-2 post administration of MEDI-573 in relation to time course of antibody concentrations in serum were evaluated during treatment.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

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。

赞助

MedImmune LLC

调查人员

  • 研究主任：Susan Perez, MD, MSc、MedImmune LLC

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。

有用的网址

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)

2009年3月9日

初级完成 (实际的)

2012年9月11日

研究完成 (实际的)

2012年9月11日

研究注册日期

首次提交

2008年12月23日

首先提交符合 QC 标准的

2008年12月30日

首次发布 (估计)

2009年1月1日

研究记录更新

最后更新发布 (实际的)

2019年3月4日

上次提交的符合 QC 标准的更新

2018年10月31日

最后验证

2018年10月1日

更多信息

与本研究相关的术语

其他研究编号

  • MI-CP184

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.

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