An Open Label Window of Opportunity Phase II Study of the FAK Inhibitor Defactinib VS-6063 in Participants With Surgical Resectable Malignant Pleural Mesothelioma.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Percentage of pFAK Inhibition in Tumor Tissue
研究概览
简要总结
This is an open label neoadjuvant (treatment with VS-6063 prior to mesothelioma surgery) study in subjects with malignant pleural mesothelioma who are eligible for surgery. Subjects will receive VS-6063 (defactinib) 400 mg twice daily for 12, 21, or 35 days or 100 mg formulation twice daily for 21 days. Pre- and post-treatment biopsies and blood samples will be collected. The purpose of this study is to assess biomarker responses from tumor tissue. The safety, pharmacokinetics, and tumor response rate to VS-6063 (defactinib) will be also be assessed.
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 malignant pleural mesothelioma that is not metastatic or unresectable
- •Eligible to undergo excisional surgery such as pleurectomy/decortication (P/DC) or any other mesothelioma surgery.
- •Localized disease. The malignancy is confined to one affected hemithorax. Mediastinal N2 lymph nodes via cervical mediastinoscopy or EBUS (endobronchial ultrasound) must be negative in order to be eligible
- •Grossly normal pulmonary, cardiac function, renal, hepatic hematologic and performance functions
- •Male or non-pregnant female
- •Age ≥ 18 years of age
- •Tissue is required prior to enrollment. If patient was diagnosed outside and tumor tissue is not available, a pleural biopsy for frozen tissue collection is required.
排除标准
- •Participants who have had chemotherapy or radiotherapy any time prior to entering the study or at any prior time for mesothelioma. Patients receiving chemotherapy type drugs for benign conditions can participate in this trial
- •History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug
- •Known history of Gilbert's Syndrome or any current hyperbilirubinemia of any cause
- •Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug
- •Subjects with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS)
- •Subjects with confirmed Hepatitis A, B or C
- •Subjects being actively treated for a secondary malignancy or any malignancy within the last 3 years, with the exception of non-melanomatous skin cancer or localized, definitively treated cervical cancer. Men under observation for local prostate cancer are also eligible if they have had stable disease for at least 1 year.
- •Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis
- •Known history of malignant hypertension
- •Uncontrolled intercurrent illness including symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations which in the opinion of the study investigators would be associated with undue risk of participation in the study
- •Use of an investigational drug within 28 days or 5 half-lives prior to first dose.
- •Pregnant or breastfeeding
研究组 & 干预措施
VS-6063 (defactinib)
Administered orally (BID) for 12, 21 or 35 days (+/- 2 days)
干预措施: VS-6063 (Drug)
结局指标
主要结局
Percentage of pFAK Inhibition in Tumor Tissue
时间窗: Cohort 1, From Baseline to Day 12; Cohort 2, From Baseline to Day 35; Cohorts 3, From Baseline to Day 21; Cohorts 3, From Baseline to day 21 day.
percentage VS-6063 (defactinib)
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), CMax
时间窗: 0-24 hours
Maximum observed plasma concentration
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), AUC (Area Under the Curve)
时间窗: 0-8 hours
Area under plasma Concentration (AUC) 0 to t
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), Median Tmax (h)
时间窗: 0-24 hours
Time to Maximum concentration (Tmax)
次要结局
- Number of Patients With at Least One Adverse Event(Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.)
- To Evaluate the Tumor Response to VS-6063 (Defactinib)(Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.)