A Phase 1b, Multicenter, Dose-Escalation Study of LY573636-sodium in Combination With Liposomal Doxorubicin in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
LY573636 + Liposomal Doxorubicin
干预措施: LY573636-sodium (Drug)
LY573636 + Liposomal Doxorubicin
干预措施: Liposomal Doxorubicin (Drug)
结局指标
主要结局
Recommended Phase 2 Dose
时间窗: Predose up to 28 days postdose in Cycle 1
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.
次要结局
- Number of Participants With Clinically Significant Events(Baseline to study completion up to 18.49 months)
- Pharmacokinetics: Maximum Concentration (Cmax) of LY573636(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)
- Number of Participants With Tumor Response(Baseline to measured progressive disease up to 4.7 months)
- Pharmacokinetics: Area Under the Curve of LY573636 Above the Albumin Corrected Threshold (AUCalb)(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)