A Phase 1 Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Subjects With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 2
- 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 increasing dose levels of VS-4718 administered in combination with gemcitabine and nab-paclitaxel in subjects with advanced cancer and to determine a recommended Phase 2 dose (RP2D) for further development of this combination in subjects with untreated advanced pancreatic cancer.
详细描述
The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-4718) in subjects with advanced cancer and Part B (Expansion) in subjects with untreated advanced pancreatic cancer.
Up to 60 evaluable subjects (i.e., subjects who complete at least 1 cycle (28 days) of therapy) will be enrolled, assuming that:
- Part A: The maximum sample size will be 6 subjects up to 4 dose levels (exclusive of replacement subjects). However, additional subjects may be added if exploration of intermediate dose level(s) of VS 4718 is warranted. The starting dose of VS-4718 will be 200mg BID.
- Part B: Up to 36 additional subjects may be enrolled at the RP2D. These subjects will be randomized at a 1:1 ratio to 1 of 2 treatment cohorts:
- Cohort 1: IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
- Cohort 2: IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed diagnosis of an advanced nonhematological malignancy (Part A) or advanced pancreatic adenocarcinoma (Part B) that is not surgically resectable
- •Eligible for treatment with nab-paclitaxel and gemcitabine on Days 1, 8, and 15 in 28-day cycles as standard therapy
- •Evaluable or measurable disease, as assessed by RECIST v1.1
- •ECOG performance status of ≤ 1
- •Adequate renal function (creatinine ≤ 1.5×ULN [upper limit of normal]) or glomerular filtration rate of ≥ 60 mL/min
- •Adequate hepatic function (total bilirubin ≤ 1.5×ULN for the institution; aspartate transaminase and alanine transaminase ≤ 2.5×ULN, or ≤ 5×ULN if due to liver involvement by tumor; albumin ≥ 3 g/dL)
- •Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100×109 cells/L; absolute neutrophil count [ANC] ≥ 1.5×109 cells/L without the use of hematopoietic growth factors)
- •Corrected QT interval (QTc) < 470 ms
- •Willing and able to participate in the trial and comply with all trial requirements
排除标准
- •Gastrointestinal (GI) condition that 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 6 months prior to the first dose of protocol therapy
- •Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of protocol therapy.
- •Part B only: Prior therapy (including investigational agents) for pancreatic cancer
- •Chemotherapy or radiotherapy within 14 days prior to first dose of protocol therapy
- •Active treatment for a secondary malignancy
研究组 & 干预措施
Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine
Part B, Cohort 1- IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
干预措施: Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine (Drug)
Part B, Cohort 2- VS-4718, nab-paclitaxel, gemcitabine
Part B, Cohort 2- IV treatment for the first 2 cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15), followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
干预措施: Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine (Drug)
Part A- VS-4718, nab-paclitaxel, gemcitabine
Part A- intravenous (IV) treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 twice-daily (BID) continuously starting on Cycle 1 Day 2. The starting dose of VS-4718 will be 200 mg BID.
干预措施: Part A- VS-4718, nab-paclitaxel, gemcitabine (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-4718 in combination with gemcitabine and nab-paclitaxel
次要结局
- Progression Free Survival(From the date of first treatment to the date of progression including death from any cause, expected average at least 5 months)
- Response rate (RR)(Every 8 weeks from baseline through the end of treatment, an expected average of 5 months])
- Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Clearance(Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle)
- Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Plasma concentration(Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle)
- Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Area under the plasma concentration versus time curve (AUC)(Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle)
- Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Maximum observed plasma concentration (Cmax)(Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle)
- Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Time to reach maximum observed concentration (Tmax)(Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle)
- Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Half life (T1/2)(Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle)