NCT02372227终止1 期
A Phase 1 Dose Escalation Study of VS-5584, a Dual PI3K/mTOR Inhibitor, Administered With a Fixed Dose of VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Relapsed Malignant Mesothelioma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 4
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate rising dose levels of VS-5584 administered in combination with a fixed dose of VS-6063 in subjects with relapsed malignant mesothelioma to determine a recommended Phase 2 dose (RP2D) for further development of this combination in this indication.
详细描述
This study is comprised of 2 sequential parts: Part 1 (Dose Escalation of VS-5584) and Part 2 (Expansion). Up to 56 evaluable subjects (i.e., subjects who complete at least 1 cycle [21 days] of therapy) will be enrolled, assuming that:
- Up to 6 dose levels of VS-5584 are studied in Part 1 (Dose Escalation of VS-5584) in combination with a fixed dose of VS-6063 at 400 mg twice daily (BID) with a maximum of 6 subjects enrolled per VS-5584 dose level, for a total of up to 36 subjects (exclusive of replacement subjects).
- Up to an additional 20 evaluable subjects may be enrolled in Part 2, the expansion portion of the study. Subjects will be treated with VS-5584 at the RP2D and schedule determined in the dose escalation portion of the study in combination with a fixed dose of VS-6063.
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
- •Histopathologically-confirmed diagnosis of malignant mesothelioma (pleural or peritoneal). Must have disease that has relapsed following at least one prior line of chemotherapy.
- •Must have received at least 3 cycles of first-line chemotherapy.
- •Evaluable or measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST).
- •Must have archival tumor tissue available for biomarker analysis. A study-specific tumor core biopsy, pleural effusion or ascites sample must be obtained prior to treatment if archival tissue is not available.
- •Performance status according to the Karnofsky Performance Scale ≥70%.
- •Fasting blood glucose of ≤ 140 mg/dL (7.8 mmol/L).
- •Adequate renal function (creatinine ≤ 1.5x upper limit of normal [ULN]) and/or glomerular filtration rate (GFR) of ≥50 mL/min.
- •Adequate hepatic function (total bilirubin ≤ 1.5x ULN; AST and ALT ≤ 3x ULN).
- •Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x10^9 cells/L; absolute neutrophil count ≥1.5x10^9 cells/L) without the use of hematopoietic growth factors.
排除标准
- •Have had a previous extra pleural pneumonectomy (EPP).
- •Gastrointestinal condition which could interfere with the swallowing or absorption of study drug.
- •Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
- •Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
- •Any evidence of serious active infection.
- •Undergoing active treatment for a secondary malignancy.
- •Cancer-directed therapy (chemotherapy, radiotherapy) within 21 days of the first dose of study drug or 5 half-lives, whichever is shorter.
- •Major surgery within 28 days prior to the first dose of study drug.
- •Acute or chronic pancreatitis.
- •Diabetes mellitus requiring insulin treatment or subjects with a hemoglobin A1C (HbA1C) >7%.
- •History or evidence of cardiac risk.
- •Known history of malignant hypertension.
研究组 & 干预措施
VS-5584 and VS-6063
Experimental
干预措施: VS-5584 and VS-6063 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: 6 months
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of VS-5584 and VS-6063 in a 21 day cycle
Safety and tolerability of the combination of VS-5584 and VS-6063
时间窗: 16 months
Dose Escalation Phase and Expansion Phase: A composite by dose level to include incidence of AEs, SAEs (overall and severity), laboratory abnormalities, ECGs, vital signs, Karnofsky Performance Status, dose interruptions and dose reductions as a measure of safety and tolerability
次要结局
- Pharmacokinetics of VS-5584 & VS-6063 plasma area under the curve from time zero to last quantifiable concentration (AUClast)(0-48 hours per patient)
- Pharmacokinetics of VS-5584 & VS-6063 time to reach maximum observed concentration (Tmax)(0-48 hours per patient)
- Pharmacokinetics of VS-5584 & VS-6063 maximum observed plasma concentration (Cmax)(0-48 hours per patient)
- Pharmacokinetics of VS-5584 & VS-6063 apparent oral clearance (CL/F)(0-48 hours per patient)
- Pharmacokinetics of VS-5584 & VS-6063 apparent volume of distribution (Vz/F)(0-48 hours per patient)
- Pharmacokinetics of VS-5584 & VS-6063 trough plasma concentration(0-48 hours per patient)
- Pharmacokinetics of VS-5584 & VS-6063 area under the curve from time zero to extrapolated infinite time (AUCO-inf)(0-48 hours per patient)
研究者
研究点 (4)
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