A Phase I Study of SAHA and Temozolomide in Children With Relapsed or Refractory Primary Brain or Spinal Cord Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 9
- 主要终点
- Maximum tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT using NCI CTCAE version 4.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating young patients with relapsed or refractory primary brain tumors or spinal cord tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help temozolomide work better by making tumor cells more sensitive to the drug.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose and/or recommended phase II dose of vorinostat in combination with temozolomide in pediatric patients with relapsed or refractory primary CNS tumors.
II. To define and describe the toxicities of this regimen in these patients.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of this regimen within the confines of a phase I 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
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed CNS malignancy at original diagnosis or relapse
- •Histologic confirmation not required for patients with intrinsic brain stem tumors, optic pathway gliomas, or pineal tumors provided CSF or serum tumor markers, including alpha-fetoprotein orbeta-HCG, are elevated
- •Recurrent or refractory spinal cord tumors allowed
- •Measurable or evaluable disease
- •No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- •Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
- •Neurological deficits must have been relatively stable for ≥ 1 week before study entry
- •Patients unable to walk due to paralysis, but who are up in a wheelchair, are considered ambulatory for the purpose of assessing performance status
- •ANC ≥ 1,000/μL
- •Platelet count ≥ 100,000/μL (transfusion independent, defined as no platelet transfusion within the past 7 days)
- •Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
- •Creatinine clearance or radioisotope GFR ≥ 70mL/min OR maximum serum creatinine based on age and/or gender as follows:
- •0.6 mg/dL (1 year of age)
- •0.8 mg/dL (2 to 5 years of age)
- •1.0 mg/dL (6 to 9 years of age)
- •1.2 mg/dL (10 to 12 years of age)
- •1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)
- •1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)
- •Bilirubin ≤ 1.5 times upper limit of normal
- •ALT ≤ 110 U/L
- •Serum albumin ≥ 2 g/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Able to swallow capsules or liquid
- •Seizure disorder allowed provided it is well controlled with nonenzyme-inducing anticonvulsants
- •No pre-existing QTc ≥ 450 msec
- •No uncontrolled infection
- •No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of study
- •Fully recovered from prior chemotherapy, immunotherapy, or radiotherapy
- •More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
- •At least 7 days since prior hematopoietic growth factors
- •At least 7 days since prior biologic agent (antineoplastic agent)
- •At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal antibodies
- •More than 2 weeks since prior local palliative radiotherapy (small port)
- •At least 6 months since prior total-body radiotherapy (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
- •At least 6 weeks since other prior substantial bone marrow radiotherapy
- •At least 3 months since prior stem cell transplantation or rescue (without TBI)
- •No evidence of active graft-vs-host disease
- •At least 2 weeks since prior valproic acid
- •No prior vorinostat
- •Prior temozolomide allowed provided there was no progressive disease during or within 1 month after completion of treatment
- •Concurrent corticosteroids allowed provided patient has been on a stable or decreasing dose for ≥ 7 days before study entry
- •No other concurrent investigational drugs
- •No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
- •No concurrent enzyme-inducing anticonvulsants
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
Arm I
Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
干预措施: temozolomide (Drug)
Arm I
Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
干预措施: diagnostic laboratory biomarker analysis (Other)
Arm I
Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT using NCI CTCAE version 4.0
时间窗: 28 days
In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.
Pharmacokinetic parameters of vorinostat in combination with temozolomide
时间窗: Pre-dose, 15 and 30 minutes, 1, 2, 4, 6, 8, and 24 hours
The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
次要结局
- Response assessed according to RECIST criteria(Up to 30 days)