Dose-Escalation Study of LY573636-sodium and Liposomal Doxorubicin in Patients With Advanced Solid Tumors
2018年12月13日 更新者：Eli Lilly and Company
A Phase 1b, Multicenter, Dose-Escalation Study of LY573636-sodium in Combination With Liposomal Doxorubicin in Patients With Advanced Solid Tumors
The goal of this study is to determine the dose of LY573636-sodium (hereafter referred to as LY573636) that can be administered safely in combination with liposomal doxorubicin in patients with advanced cancer who have failed a prior treatment.
The study consists of a dose escalation phase to the maximum tolerated dose (MTD) and a dose confirmation phase in patients with platinum resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have never been treated with doxorubicin.
研究概览
研究类型
介入性
注册 (实际的)
31
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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Arizona
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Scottsdale、Arizona、美国、85258
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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California
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Encinitas、California、美国、92024
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Oklahoma
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Oklahoma City、Oklahoma、美国、73104
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Tennessee
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Memphis、Tennessee、美国、38119
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Washington
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Seattle、Washington、美国、98195
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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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:
- You must have a histologically confirmed solid malignancy that is unresectable and/or metastatic which has progressed after receiving standard approved chemotherapy
- You must have a solid malignancy for which an anthracycline-based regimen is felt to be a reasonable treatment option
- You must have measurable disease or non-measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
- You must have a serum albumin level greater than or equal to 3.0 grams/deciliter (g/dL) (30 g/L)
- You must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- You must have tumor progression after receiving standard/approved chemotherapy
- You must be reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures
- Women must be sterile, post-menopausal or on a contraception and men must be sterile or on contraception
- Your test results assessing the function of your blood, kidneys, liver, and heart are satisfactory
- Ovarian patients in the confirmation phase must have failed to achieve at least a partial response to a first-line platinum-based therapy (platinum-refractory) or have progression in less than 6 months after a response to a first-line platinum-based therapy (platinum-resistant)
- Ovarian patients in the confirmation phase must have measurable disease by RECIST
- Ovarian patients in the confirmation phase must be liposomal doxorubicin or doxorubicin naive and not amendable to curative therapy
Exclusion Criteria:
- You cannot have received other investigational drugs within the last 28 days
- You cannot have other on-going serious illnesses including active bacterial, fugal, or viral infections
- You cannot have current hematologic malignancies, acute or chronic leukemia, or brain metastasis
- You cannot currently be receiving warfarin (Coumadin®) therapy
- You cannot have known positive test results in human immunodeficiency, hepatitis B surface antigen or hepatitis C antibodies
- You cannot have a history of cardiac disease or clinical evidence of congestive heart failure
- Ovarian patients in the confirmation phase who have received 2 or more cytotoxic regimens for platinum-resistant disease
- You cannot currently be receiving amiodarone, quinidine, propofol, and clozapine
- If you are taking esomeprazole or pantoprazole you must be able to stop taking this medication within 72 hours before and after LY573636 administration
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
- 介入模型：顺序分配
- 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：LY573636 + Liposomal Doxorubicin
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Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28-day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, cumulative dose of 550 milligrams per square meter (mg/m²) of liposomal doxorubicin or doxorubicin is reached, or other withdrawal criterion is met.
其他名称：
40 mg/m² on Day 1, given intravenously of each 28-day cycle Participants may continue on study drug until disease progression, unacceptable toxicity, cumulative dose of 550 mg/m² of liposomal doxorubicin or doxorubicin is reached, or other withdrawal criterion are met. |
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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Recommended Phase 2 Dose
大体时间：Predose up to 28 days postdose in Cycle 1
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Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which is corrected for the participant's predose albumin to identify the albumin-corrected exposure range of LY 573636 when combined with liposomal doxorubicin.
MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) in the first 28-day cycle of treatment.
DLT is an adverse event (AE) that is likely related to the study drug or combination and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity; Gr 3 nonhematologic toxicity (excluding controllable nausea/vomiting or diarrhea and alopecia); Gr 3 electrolyte toxicity that is not resolved with standard treatments.
Those who enter the study with Gr 2 hepatic enzyme abnormalities, DLT for an isolated Gr 3 hepatic enzyme abnormality is determined by investigators; a DLT can be declared if a participant experiences increasing toxicity during treatment.
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Predose up to 28 days postdose in Cycle 1
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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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Number of Participants With Clinically Significant Events
大体时间：Baseline to study completion up to 18.49 months
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Clinically significant events are defined as serious adverse events (SAEs), regardless of causality, during the study including the 30-day follow-up period.
A summary of SAEs and other nonserious adverse events is located in the Reported Adverse Event section.
Death due to progressive disease was not considered as an SAE.
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Baseline to study completion up to 18.49 months
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Pharmacokinetics: Maximum Concentration (Cmax) of LY573636
大体时间：Predose, 30 minutes (min), 2 hours (h), 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3
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Predose, 30 minutes (min), 2 hours (h), 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3
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Number of Participants With Tumor Response
大体时间：Baseline to measured progressive disease up to 4.7 months
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Number of participants with tumor response = number of participants with complete response (CR) + number of participants with partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines.
CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in the sum of longest diameter of target lesions.
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Baseline to measured progressive disease up to 4.7 months
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Pharmacokinetics: Area Under the Curve of LY573636 Above the Albumin Corrected Threshold (AUCalb)
大体时间：Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3
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LY573636 has been found to be highly bound to albumin.
AUCalb is a surrogate measure of exposure to unbound (free) LY573636.
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Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 1; Predose, 30 min, 2 h, 4 h, 166 h, 360 h and 698 h postdose in Cycle 2; Predose, 166h, 360h and 698 h postdose in Cycle 3
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其他结果措施
结果测量 |
大体时间 |
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Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment
大体时间：From date of randomization until up to 30 days post study treatment discontinuation, assessed up to 4.7 months
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From date of randomization until up to 30 days post study treatment discontinuation, assessed up to 4.7 months
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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。
调查人员
- 研究主任：Call 1-877-CTLILLY (1-877-285-4559) or 317-651-4559 Mon. - Fri. 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)、Eli Lilly and Company
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
2009年1月1日
初级完成 (实际的)
2012年2月1日
研究完成 (实际的)
2012年2月1日
研究注册日期
首次提交
2010年10月1日
首先提交符合 QC 标准的
2010年10月4日
首次发布 (估计)
2010年10月5日
研究记录更新
最后更新发布 (实际的)
2019年1月4日
上次提交的符合 QC 标准的更新
2018年12月13日
最后验证
2018年12月1日
更多信息
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.
实体瘤的临床试验
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AstraZeneca招聘中Adv Solid Malig - H&N SCC、ATM Pro / Def NSCLC、胃癌、乳腺癌和卵巢癌西班牙, 美国, 比利时, 英国, 法国, 匈牙利, 加拿大, 大韩民国, 澳大利亚