A Phase 1 Study of PXD101 in Combination With Bortezomib (PS-341) in Patients With Advanced Solid Tumors and Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of PXD101 in combination with bortezomib
研究概览
简要总结
This phase I trial is studying the side effects and best dose of PXD101 and bortezomib in treating patients with advanced solid tumors or lymphomas. PXD101 and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PXD101 may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving PXD101 together with bortezomib may kill more cancer cells.
详细描述
OBJECTIVES:
I. Evaluate the safety profile and determine the maximum tolerated dose of PXD101 in combination with bortezomib in patients with advanced solid tumors or lymphomas.
II. Determine the pharmacokinetics of the combination of PXD101 and bortezomib in these patients.
III. Evaluate selected biomarkers of drug effect in these patients. IV. Evaluate the activity of this regimen, in terms of objective response rate, in these patients.
OUTLINE: This is a dose-escalation study.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed solid tumor or lymphoma that is refractory to standard therapy or for which no standard therapy exists
- •No active, untreated, or symptomatic brain metastases
- •Patients with treated brain metastases are eligible provided metastasis are stable and the patient is off all steroids and anticonvulsants
- •ECOG performance status 0-2
- •Life expectancy ≥ 12 weeks
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 1.5 mg/dL
- •AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of liver metastases)
- •Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101, bortezomib, boron, or mannitol
- •No peripheral neuropathy > grade 1
- •No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Psychiatric illness or social situation that would preclude study requirements
- •No significant cardiovascular disease, including any of the following:
- •Myocardial infarction within the past 6 months
- •New York Heart Association class III-IV heart failure
- •Unstable angina pectoris
- •Uncontrolled hypertension
- •Condition requiring antiarrhythmic therapy
- •Ischemic or severe valvular heart disease
- •Acute ischemia or active conduction system abnormalities by ECG
- •No marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval > 500 msec), long QT syndrome, or required use of concurrent medication during PXD101 administration that may cause torsade de pointes
- •No severe medical or psychiatric problems of that would preclude study compliance
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin C)
- •At least 4 weeks since prior radiotherapy and recovered
- •At least 2 weeks since prior palliative radiotherapy to sites involving < 35% of bone marrow reserve
- •At least 4 weeks since prior investigational agents
- •At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
- •No prior stem cell or bone marrow transplantation
- •No concurrent radiotherapy or immunotherapy
- •No concurrent hormonal therapy
- •Luteinizing hormone-releasing hormone agonists, selective estrogen receptor modulators, or aromatase inhibitors as chronic maintenance therapy allowed
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent investigational agents
- •No other concurrent anticancer agents or therapies
排除标准
- 未提供
研究组 & 干预措施
PXD101 in Combination with Bortezomib (PS-341)
Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1).
干预措施: belinostat (Drug)
PXD101 in Combination with Bortezomib (PS-341)
Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1).
干预措施: bortezomib (Drug)
PXD101 in Combination with Bortezomib (PS-341)
Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1).
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum tolerated dose of PXD101 in combination with bortezomib
时间窗: Day 21
Defined as the dose level below that which results in drug-related dose limiting toxicity (DLT) in \>= 2 of 6 new patients.
Frequency and severity of treatment-related adverse events graded per NCI CTCAE version 3.0
时间窗: Day 21
Changes in biological markers (p21, cleaved PARP, IkB, p65 Rel A, p-AKT, p-ERK and apoptosis) from pre- to post-treatment
时间窗: Baseline and day 21
Objective response rate
时间窗: 4 weeks
次要结局
- Pharmacokinetics of the combination of PXD101 with bortezomib(Baseline, end of infusion, then 15 minutes, 30 minutes, 1, 2, 4 and 6 hours from the end of infusion (days 1 and 2))