A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 193
- 试验地点
- 43
- 主要终点
- Peak Plasma Concentration (Cmax) of MGCD516
研究概览
简要总结
MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles.
During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations.
Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.
详细描述
During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.
During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon the following cancer diagnosis:
Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL.
Head and neck squamous cell carcinoma with genetic alterations in MET.
Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.
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
- •Metastatic or unresectable solid tumor malignancy
- •Standard treatment is not available
- •Adequate bone marrow and organ function
排除标准
- •History of a significant cardiovascular illness
- •Prolonged corrected QT (QTc) interval
- •Left ventricular ejection fraction < 40%
- •Symptomatic or uncontrolled brain metastases
- •Other active cancer
研究组 & 干预措施
MGCD516
MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles
干预措施: MGCD516 (Drug)
结局指标
主要结局
Peak Plasma Concentration (Cmax) of MGCD516
时间窗: Up to 72 hours
Type of dose limiting adverse event
时间窗: Up to 3 weeks on treatment
Area under the plasma concentration versus time curve (AUC) of MGCD516
时间窗: Up to 72 hours
次要结局
- Kind of metabolites of MGCD516 in blood plasma(Up to 9 weeks on treatment)
- Concentration of selected marker proteins in blood plasma(Up to 9 weeks on treatment)
- Percent of patients having objective disease response to treatment(Up to 1 year on treatment)