A Phase I, Multi-center, Open-Label, Dose-Escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of PRLX 93936 Administered Intravenously Daily for Five Days Followed by a 23-Day Rest Period in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 3
- 主要终点
- Clinical laboratory tests
研究概览
简要总结
The purpose of this study is to test the safety of PRLX 93936 and see what kind of effect it has on patients and their cancer. This study will also determine the highest dose of PRLX 93936 that can be given without causing adverse side effects and the dose of PRLX 93936 that should be used in future studies.
详细描述
This study will assess the safety, pharmacokinetics, and pharmacodynamics of PRLX 93936 administered intravenously over 1 hr daily for 5 days in patients with advanced solid tumors. Patients will be evaluated prior to dosing, during dosing and following dosing, on a 28-day cycle. Tumor response will be evaluated every other cycle.
Three patients will be assigned per dose level until the Maximum Tolerated Dose (MTD) is reached or a a Dose-Limited Toxicity (DLT) is encountered. Sequential cohorts of three patients will be treated with escalating doses until the Maximum Tolerated Dose (MTD) is reached.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed solid tumors
- •Tumor progression after receiving standard/approved chemotherapy and for whom no available treatment provides clinical benefit
- •One or more metastatic tumors measurable on a CT scan or MRI per RECIST criteria
- •ECOG performance 0-1
- •Life expectancy of at least 3 months
- •Age >/= 18 years
- •A negative pregnancy test (if female of child-bearing potential)
- •Acceptable liver function:
- •Bilirubin </= 1.5 times the Upper Limit of Normal (ULN)
- •AST (SGOT), ALT (SGPT) and Alkaline phosphatase </= 2.5 times ULN (if liver metastases are present, then </= 5 times ULN is allowed)
- •Acceptable renal function:
- •Serum creatinine within normal limits, OR calculated creatinine clearance >/= 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal
- •Acceptable hematologic status:
- •Granulocyte count >/= 1500 cells/mm3
- •Platelet count >/= 100,000 (plt/mm3)
- •Hemoglobin >/= 9.0 g/dL
- •Urinalysis: no clinically significant abnormalities
- •Acceptable coagulation status:
- •PT within normal limits
- •aPTT within normal limits
- •Completed any chemotherapy, major surgery, or irradiation at least four weeks before enrollment in this study (six weeks for mitomycin-C or nitrosoureas, and two weeks for "targeted" therapies such as kinase inhibitors). Patient must have recovered from all toxicities incurred as a result of previous therapy.
- •QT intervals of QTC </= 450 msec for men and </= 470 msec for women (as measured by Hodges equation)
- •Left ventricular ejection fraction >/= 50% by 2D Echocardiogram (or > institutional lower limits of normal)
排除标准
- •NYHA Class III or IV, cardiac disease, myocardial infarction within the past six months, unstable arrhythmia, or evidence of ischemia on ECG
- •Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- •Pregnant or nursing women
- •Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within four weeks prior to study entry (six weeks for mitomycin-C or nitrosoureas and two weeks for targeted therapies such as kinase inhibitors).
- •Unwillingness or inability to comply with protocol procedures
- •Known current infection with HIV, hepatitis B or hepatitis C
- •Currently receiving any other investigational agent
- •Currently receiving medications metabolized by the cytochrome P450 3A4 enzyme pathway
- •Presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with brain metastases which are well controlled (patients not taking dexamethasone or anti-seizure medication >/= three months after treatment) may be enrolled.
- •Any other severe concurrent disease, which in the judgement of the investigator would make the patient inappropriate for the study
- •Diagnosis of hypertension
- •Previously enrolled in this trial
研究组 & 干预措施
PRLX 93936
干预措施: PRLX 93936 (Drug)
结局指标
主要结局
Clinical laboratory tests
时间窗: Weekly
Vital signs
时间窗: Daily during dosing, then weekly during followup
Electrocardiograms (ECGs)
时间窗: Multiple times during dosing, then weekly during followup
Echocardiograms (ECHO)
时间窗: Baseline and every other cycle
次要结局
- Tumor assessment(Baseline and every other cycle)
- Blood sampling for pharmacokinetics(Days 1 and 5 of dosing)