An Open Label, Multiple Centers Phase Ib/II Study of APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Overall Response Rate (Applicable for: phase II stage) .
研究概览
简要总结
This study is a two stage study consisting of a dose escalation phase Ib and a phase II study which include subjects with previously-treated, advanced pancreatic adenocarcinoma. Dose Limiting Toxicities (DLTs) and maximum tolerated dose (MTD) of APG1387 in combination with nab-paclitaxel and gemcitabine will be evaluated in the dose escalation phase Ib. Safety and efficacy of APG1387 plus gemcitabine and nab-paclitaxel will be evaluated in phase II.
详细描述
The ability of tumor cells to evade apoptosis is currently a major problem in anti-tumor therapy. IAPs are an important class of apoptosis-regulating proteins. APG-1387, a potent bivalent SMAC mimetic, small molecule of IAP inhibitor, which could inhibit pancreatic cancer proliferation as monotherapy and in combination with chemotherapy through apoptosis pathway.
It's an open label, multiple centers phase Ib/II Study. Safety and tolerability of APG1387 combined with nab-paclitaxel and gemcitabine will be evaluated in phase Ib in previously-treated, advanced pancreatic adenocarcinoma patients. Efficacy and tolerability will be evaluated in phase II study in first line standard treatment failed metastatic pancreatic adenocarcinoma patients.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be ≥18 years of age at time of informed consent
- •Able to comply with the study protocol, in the investigator's judgment
- •Expected survival ≥ 3 months
- •Histology or cytology confirmed as advanced pancreatic adenocarcinoma, and:
- •Standard treatment failed or intolerant to standard treatment(Phase Ib);
- •First line standard treatment failed (Phase II).
- •Adequate organ function.
- •Subjects must have at least one measurable lesion evaluated by Computed Tomography (CT) scan on RECIST ver.1.1 at pre-treatment
排除标准
- •Has had chemotherapy, radiation, target or other antitumor therapy within 14 days prior to the first dose of study drug.
- •Has received an investigational agent or used an investigational device within 28 days of the first dose of study drug.
- •Has received a therapy with TNFα within 28 days of the first dose of study drug.
- •Known active central nervous system involvement.
- •Has received IAP-inhibitor before.
- •Has had major surgery within 28 days of dosing of investigational agent, or minor surgery within 14 days.
- •Patients with clinically evident Hepatitis B surface antigen (HBs) positive, Hepatitis C virus (HCV) antibody positive, Human Immunodeficiency Virus (HIV) antibody positive.
- •Pregnant or breastfeeding (lactating) women.
- •Other situations that investigator think not suit for study.
研究组 & 干预措施
APG1387 in combination with Gemcitabine and Nab-Paclitaxel
干预措施: APG-1387 for Injection (Drug)
APG1387 in combination with Gemcitabine and Nab-Paclitaxel
干预措施: Gemcitabine (Drug)
APG1387 in combination with Gemcitabine and Nab-Paclitaxel
干预措施: Nab paclitaxel (Drug)
结局指标
主要结局
Overall Response Rate (Applicable for: phase II stage) .
时间窗: Up to 2 years.
Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Dose Limiting Toxicities (DLT) of combination therapy (Applicable for: phase Ib stage ).
时间窗: 28 days.
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.
次要结局
- Duration of Response (DOR)(Up to 2 years.)
- Overall Survival (OS)(Up to 2 years.)
- Progression Free Survival (PFS)(Up to 2 years.)
- Maximum plasma concentration (Cmax)(28 days.)
- Area under the plasma concentration versus time curve (AUC)(28 days.)
- Adverse events(Up to 2 years.)