A Phase I Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Subjects With Metastatic Non-Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 48
- 试验地点
- 5
- 主要终点
- Assess the safety and tolerability of VS-4718 in subjects with metastatic non-hematologic malignancies
研究概览
简要总结
This is a Phase I, open-label, multicenter, dose-escalation trial of VS-4718, a focal adhesion kinase inhibitor, in subjects with metastatic non-hematologic malignancies. This clinical study is comprised of 2 parts: Part 1 (Dose Escalation) and Part 2 (Expansion). The purpose of this study is to evaluate the safety (including the recommended Phase II dose), pharmacokinetics (the amount of VS-4718 in your blood) and the anti-cancer activity of VS-4718. The pharmacodynamic effects (genes or proteins that may predict or show how your body may respond to VS-4718) will also be examined in tumor biopsies and blood samples.
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
- •Age ≥ 18 years.
- •Histopathologically confirmed diagnosis of a metastatic non-hematologic malignancy.
- •ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2
- •Adequate renal function
- •Adequate hepatic function (total bilirubin ≤ 1.5x ULN (upper limit of normal) for the institution; AST [aspartate transaminase] and ALT [alanine transaminase] ≤ 3x ULN, or ≤ 5x ULN if due to liver involvement by tumor).
- •Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100 x10 9 cells/L; absolute neutrophil count ≥ 1.5x10 9 cells/L
- •Corrected QT interval (QTc) < 470 ms
- •Subjects must have at least one tumor lesion that is suitable for repeat biopsy, and must agree to two tumor biopsies (pre- and post- treatment).
- •Willing and able to participate in the trial and comply with all trial requirements.
排除标准
- •Gastrointestinal (GI) condition which could interfere with the swallowing or absorption of study medication.
- •Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
- •History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months.
- •Known history of stroke or cerebrovascular accident within 6 months.
- •Subjects being actively treated for a secondary malignancy.
研究组 & 干预措施
VS-4718
Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.
干预措施: VS-4718 (Drug)
结局指标
主要结局
Assess the safety and tolerability of VS-4718 in subjects with metastatic non-hematologic malignancies
时间窗: Expected average of 12 weeks from start of treatment to end of treatment
Serious Adverse events, Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECGs as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) V4.03. A Safety monitoring committee will review safety information.
Establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of VS-4718 in subjects with metastatic non-hematologic malignancies
时间窗: From start of treatment to end of cycle 1 (4 week cycles)
The RP2D will be determined based on the maximum tolerated dose (MTD) of VS-4718 as determined by number of participants with dose limiting toxicities related to VS-4718. Observations related to pharmacokinetics, pharmacodynamics, and any VS-4718 related toxicities may be included in the rationale supporting the RP2D and will not exceed the MTD.
次要结局
- Evaluate biomarkers of VS-4718 activity(Day 1 and Day 15 of treatment)
- Assess the pharmacokinetics of VS-4718(Time points on Day 1, 2, 8, 15, 16, and 29)
- Evaluate the efficacy of VS-4718(Every 8 weeks to end of treatment, expected average of 16 weeks)
- Evaluate duration of response to VS-4718 compared with duration of response to prior therapy.(Expected average of 16 weeks from start of treatment to end of treatment)
- Examine if the tumor expression status of pFAK and other plasma biomarkers correlates with response to VS-4718 therapy(From start of treatment to end of treatment, an expected average of 16 weeks)