A Phase I Study of the Safety and Tolerability of Single Agent MSI-1436C in Metastatic Breast Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Maximally Tolerated Dose (MTD) of MSI-1436
研究概览
简要总结
This is a Phase I, open-label, dose escalation study. MSI-1436 will be administered as a single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
详细描述
This is a Phase I, open-label, dose escalation study. MSI-1436 will be administered as a single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will be enrolled according to a standard Phase I Fibonacci design to receive MSI-1436. Drug infusions will last approximately 2 hours. If a subject has a dose-limiting toxicity (DLT) at any time during the study, MSI-1436 will be held and either re-started or discontinued in that subject as per the Dose Adjustments and Toxicities Guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed, witnessed, and dated Institutional Review Board (IRB) approved Informed Consent Form (ICF).
- •Pathologically confirmed metastatic breast cancer with measurable disease. Metastatic sites must be measurable on CT, MRI, or FDG-PET/CT as per the revised RECIST v1.1 criteria or measurable disease on physical examination.
- •A metastatic site must be biopsy proven
- •Life expectancy ≥3 months.
- •Patients enrolled must have received 2 or more lines of therapy and all patients with HER2 expressing tumors must have received HER2 targeted therapy.
- •Female Age ≥18 years.
- •Stable brain metastasis is permitted. This is not considered measurable disease.
- •Stable brain metastasis is defined as no change on CT scan or MRI for minimum of 2 months AND no change in steroid dose for a minimum of 4 weeks
- •A negative serum pregnancy test, if female of reproductive potential. Reproductive potential defined as age < 55 or with no menses for < 1 year
- •Screening laboratory values as follows:
- •Total bilirubin ≤1.5 times upper limit of normal (ULN). Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvate transaminase)≤ 2.5 times ULN.
- •Serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥60 mL/min. Absolute neutrophil count >1,500 cells/mm
- •Platelet count ≥100,000 plt/mm
- •Hemoglobin ≥ 8 g/dL. Non-diabetic
排除标准
- •Pregnant or breast-feeding
- •ECOG Performance Status greater than 2
研究组 & 干预措施
MSI-1436C (Trodusquemine) 44 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 44 mg/m2 . Drug infusions will last approximately 2 hours.
干预措施: MSI-1436C (Drug)
MSI-1436C (Trodusquemine) 20 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 20 mg/m2. Drug infusions will last approximately 2 hours.
干预措施: MSI-1436C (Drug)
MSI-1436C (Trodusquemine) 26 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 26 mg/m2. Drug infusions will last approximately 2 hours.
干预措施: MSI-1436C (Drug)
MSI-1436C (Trodusquemine) 34 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 34 mg/m2 . Drug infusions will last approximately 2 hours.
干预措施: MSI-1436C (Drug)
MSI-1436C (Trodusquemine) 57 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 57 mg/m2. Drug infusions will last approximately 2 hours.
干预措施: MSI-1436C (Drug)
MSI-1436C (Trodusquemine) 74 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 74 mg/m2 . Drug infusions will last approximately 2 hours.
干预措施: MSI-1436C (Drug)
MSI-1436C (Trodusquemine) 96 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 96 mg/m2 . Drug infusions will last approximately 2 hours.
干预措施: MSI-1436C (Drug)
结局指标
主要结局
Maximally Tolerated Dose (MTD) of MSI-1436
时间窗: one year
Subjects will be enrolled according to a standard Phase I Fibonacci design to receive MSI-1436C. If a subject has a dose-limiting toxicity (DLT) at any time during the study, MSI-1436C will be held and either re-started or discontinued in that subject as per the Dose Adjustments and Toxicities Guidelines.
次要结局
- Peak plasma concentration of the drug after administration (cmax)(one year)
- Area under the plasma concentration versus time curve (AUC)(one year)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(one year)
- Time required for the concentration of MSI-1436C to reach half of its original value, or half life (t1/2)(one year)
- Time to reach cmax(one year)
- response rates(one year)
研究者
Daniel Budman
Director Translational Research, Cancer Institute
Northwell Health