A Phase I/II Trial of AEZS-108 in Locally Advanced Unresectable or Metastatic Luteinizing Hormone-releasing Hormone(LHRH) Positive Urothelial Carcinoma Patients Who Failed Platinum Based Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
The purpose of this study is to determine the appropriate dose of AEZS-108 to treat patients with a tumor of the urinary system.
详细描述
AEZS-108 is an investigational drug, combining luteinizing hormone-releasing hormone (LHRH), an hormone and doxorubicin (a drug approved to treat different types of cancer).
Some tumors, such as those found in the urinary system (also called urothelial carcinomas), have LHRH hormone receptors to which the LHRH hormone part of AEZS-108 is attracted.
AEZS-108 is expected to work by accumulating mostly on the surface of cancer cells that have LHRH hormone receptors and by delivering doxorubicin more directly into the cells to kill them. This would allow the use doxorubicin at lower doses and thus would cause less toxicity.
In the first part of the study, the appropriate dose of AEZS-108 will be determined based on its side effects. The best dose will be the highest one without severe side effects.
In the second part of the study, this best dose of AEZS-108 will be given to determine its efficacy to stop the tumor from progressing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma
- •Expression of LHRH receptors confirmed by immunohistochemistry on archival cancer tissue
- •Measurable disease on radiological studies
- •Patients with Locally advanced unresectable or metastatic urothelial carcinoma
- •Documented progression on at least one prior chemotherapy regimen which must have incorporated platinum based therapy
- •Left ventricular ejection fraction (EF) > 50%
- •Eastern cooperative oncology group (ECOG) status of 0, 1 or 2
- •Adequate bone marrow, renal and hepatic function
排除标准
- •Prior treatment with or allergy to any components of AEZS-108
- •Active second malignancies other than non-melanoma skin cancers
- •Ongoing use of an LHRH agonist (or antagonist)
- •Presence of an active infection or fever > 38.5 C, parenchymal brain metastases or uncontrolled intercurrent illness
- •Prior exposure to anthracyclines or anthracenediones including doxorubicin, daunorubicin, and mitoxantrone
- •Patients who received radiotherapy within 4 weeks of entry
- •Major surgery within the last 4 weeks and minor surgery in last 7 days
研究组 & 干预措施
Phase 1 - Cohort 1
Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).
Patients will be enrolled in cohorts of 3 at a specified AEZS-108 dose beginning with 160mg/m^2. Enrollment will be suspended until all members of a cohort have been observed for dose limiting toxicities (DLT) for a period of 3 weeks (1 cycle of AEZS-108) from initial treatment with AEZS-108. Dose escalation will proceed within each cohort according to a specific scheme where DLT is defined.
干预措施: AEZS-108 (Drug)
Phase 1 - Cohort 2
Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).
干预措施: AEZS-108 at MTD (Drug)
Phase 1 - Cohort 3
Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).
干预措施: AEZS-108 (Drug)
Phase 1 - Cohort 4
Determination of maximum tolerated dose (MTD) and recommended parenteral administration dosing for AEZS-108 in 4 sequential cohorts of patients (3-6 patients/cohort).
干预措施: AEZS-108 (Drug)
Phase 2
AEZS-108 at MTD to determine efficacy in up to 40 patients.
干预措施: AEZS-108 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Day 1 of each 21-day cycle
Toxicity per Common Terminology Criteria for Adverse Events (CTCAE).
次要结局
- Objective tumor response(Within 5 days of cycle 4, then every 3 cycles)
- Pharmacokinetics (PK)(cycle 1)
- Circulating tumor cell (CTC) levels(last cycle)
- Progression-free survival (PFS)(last cycle)
- Overall survival(last cycle)