A Phase I, Open Label, Multi-Center, Dose Escalation Study of the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Properties of Orally Administered AT-406 in Patients With Advanced Solid Tumors and Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 3
- 主要终点
- Maximally Tolerated Dose
研究概览
简要总结
The purpose of this study is to determine the safety profile and the maximum dose of Debio 1143 (AT-406) that can be given to humans. This study is also designed to measure how much Debio 1143 (AT-406) gets into the blood stream (pharmacokinetics), and how Debio 1143 (AT-406) interacts with proteins related to cancer that the drug is targeted to affect (pharmacodynamics).
详细描述
Ascenta Therapeutics, Inc. is conducting a clinical trial of the compound Debio 1143 (AT-406), a small molecule second mitochondria-derived activator of caspase C (Smac) mimetic. In vivo and in vitro studies have demonstrated that Debio 1143 (AT-406) induces cell death in several tumor models by inhibiting XIAP (X linked IAP), cIAP-1 (cellular IAP-1) and cIAP-2 (cellular IAP-2), thus releasing initiator and effector caspases to promote apoptosis. This protocol is a Phase I, dose-escalation, open-label, multi-center study conducted in patients with advanced solid tumors and lymphomas to evaluate the safety, tolerability and pharmacology of Debio 1143 (AT-406) in humans when administered orally.
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
- •Histologically confirmed solid tumor or lymphoma;
- •Locally advanced or metastatic disease for which no life prolonging therapy is available and no standard therapy is judged appropriate by the investigator;
- •Eastern Cooperative Oncology Group Performance Status ≤ 1;
- •Adequate hematologic function as indicated by, ANC ≥ 1,500/mm3, Hgb >9.0 g/dL, platelet count ≥ 100,000/mm3
- •Adequate renal and liver function as indicated by serum creatinine ≤ 1.0 x ULN or creatinine clearance of > 60 cc/min, serum albumin ≥ 3.0 gm/dL, total bilirubin < 1.0 x ULN, AST and ALT ≤ 2.5 x ULN ; Alkaline phosphatase ≤2.5 x ULN
- •Negative Hepatitis B and Hepatitis C testing;
- •QTc interval ≤450ms.
排除标准
- •Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry. Patients who have received prior radiotherapy must have discontinued steroids for 14 days prior to study entry and be clinically stable;
- •Not recovered to ≤ Grade 1 toxicity from prior radiotherapy or chemotherapy agents;
- •Use or requirement for use of aspirin or aspirin containing products with >81 mg of aspirin per day;
- •History of gastrointestinal bleeding within 1 year;
- •History of diabetes mellitus requiring treatment with oral agents or insulin;
- •Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation;
- •Known or suspected Wilson's Disease, or other conditions that affect copper accumulation or regulation;
- •Prior treatment with IAP inhibitors.
研究组 & 干预措施
Debio 1143 (AT-406)
Open label study. All patients participating in the study will receive Debio 1143 (AT-406).
干预措施: Debio 1143 (AT-406) (Drug)
结局指标
主要结局
Maximally Tolerated Dose
时间窗: 1 cycle, or any time during treatment
The primary endpoint of this study is to characterize the safety, and determine the maximum tolerated dose and schedule of Debio 1143 (AT-406) when administered to patients with advanced cancer. Patients will receive Debio 1143 (AT-406) on days 1-5, and 15-19 of a 28 day cycle, days 1-5 of a 21 day cycle, or days 1-14 of a 21 day cycle. For the purpose of determining the MTD, dose limiting toxicities will be evaluated at any time. For the purpose of dose escalation, dose limiting toxicities will be evaluated through the end of 1 cycle.
次要结局
- Pharmacodynamic(Cycle 1)
- Pharmacokinetic(Days 1-5 of Cycle 1)
- Efficacy(After a minimum of 2 cycles.)
- Correlation of Efficacy to Pharmacokinetic and/or Pharmacodynamic Effects of Debio 1143 (AT-406)(Anytime during Debio 1143 (AT-406) treatment)