An Open-label Phase Ib Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Maximum Tolerated Dose of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin 30 mg/m2 Given Every 3 Weeks in Subjects With Mesothelin-expressing Platinum-resistant Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 65
- 试验地点
- 9
- 主要终点
- Incidence of serious and non-serious adverse events (AEs)
研究概览
简要总结
Anetumab ravtansine is developed for the treatment of patients with recurrent platinum-resistant ovarian cancer. The purpose of the proposed trial is to identify the maximum tolerated dose of anetumab ravtansine that could be safely combined with pegylated liposomal doxorubicin in this indication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subjects with locally invasive or metastatic, epithelial ovarian, fallopian tube, or primary peritoneal cancer
- •Subjects must provide samples of tumor tissue
- •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Subjects with low-grade ovarian, fallopian tube, or Primary peritoneal cancer
- •Women who are pregnant or breast feeding
- •Subjects who have an active hepatitis B virus or hepatitis C virus infection requiring treatment as defined in the protocol
研究组 & 干预措施
Anetumab ravtansine
Anetumab ravtansine in combination with pegylated liposomal doxorubicin in subjects with mesothelin-expressing platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer. Increase/Decrease of Anetumab ravtansine until maximum tolerated dose identified.
干预措施: Anetumab ravtansine (BAY94-9343) (Drug)
Anetumab ravtansine
Anetumab ravtansine in combination with pegylated liposomal doxorubicin in subjects with mesothelin-expressing platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer. Increase/Decrease of Anetumab ravtansine until maximum tolerated dose identified.
干预措施: Pegylated Liposomal Doxorubicin (Drug)
结局指标
主要结局
Incidence of serious and non-serious adverse events (AEs)
时间窗: Up to 6 months
Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin when given every three weeks
时间窗: Up to 6 months, minimum: 1 cycle (=21days)
MTD is defined as the highest dose of anetumab ravtansine administered in combination with pegylated liposomal doxorubicin that can be given such that not more than 1 of 6 subjects at a given dose level experiences a dose-limiting toxicity (DLT).
次要结局
- Cmax of total pegylated liposomal doxorubicin(At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose, beginning on day 1 of cycle 1)
- Incidence of patients with CR, PR, SD or PD according to RECIST 1.1(Up to 17 months or until discontinuation of study, whichever comes first)
- Cmax (maximum drug concentration in plasma after first dose administration) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)(At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1)
- AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)(At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1)
- AUC of total pegylated liposomal doxorubicin(At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1)
- Incidence of positive neutralizing antibody titer(Up to 17 months or until discontinuation of study, whichever comes first)
- AUC(0-tlast) (AUC from time zero to the last data point > lower limit of quantification) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me)(At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1)
- AUC(0-tlast) of total pegylated liposomal doxorubicin(At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1)
- Incidence of positive anti-drug antibody titer(Up to 17 months or until discontinuation of study, whichever comes first)