A Phase I Study of Vorinostat and Bortezomib in Children With Refractory or Recurrent Solid Tumors, Including CNS Tumors and Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 6
- 主要终点
- Maximum-tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT according to NCI CTCAE version 3.0
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 bortezomib in treating young patients with refractory or recurrent solid tumors, including CNS tumors and lymphoma. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose and/or recommended phase II dose of vorinostat in combination with bortezomib in pediatric patients with refractory or recurrent solid tumors, including central nervous system tumors and lymphoma.
II. To define and describe the toxicities of this regimen in these patients. III. To characterize the pharmacokinetics 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 solid tumors, including CNS tumors or lymphoma
- •Histological confirmation not required for the following diagnoses
- •Intrinsic brain stem tumors
- •Optic pathway gliomas
- •Pineal tumors and elevations of cerebral spinal fluid or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin, allowed
- •Relapsed or refractory disease
- •Must have measurable or evaluable tumor
- •No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- •Karnofsky performance status (PS) 60-100% for patients > 16 years of age OR Lansky PS60-100% for patients ≤ 16 years of age
- •Neurologic deficits inpatients with CNS tumors must have been relatively stable for a minimum of 1week
- •Patients who are unable to walk because ofparalysis, but who are up in a wheelchair, will be considered ambulatory for thepurpose of assessing the performance score
- •ANC ≥ 1,000/μL
- •Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within the past 7 days)
- •Patients with known bone marrow metastatic disease allowed provided they meet the blood count criteria and are not known to be refractory to platelet transfusion
- •Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- •Patients with known bone marrow metastatic disease allowed provided they meet the blood count criteria and are not know to be refractory to RBC or platelet transfusion
- •Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:
- •0.6 mg/dL (1 to < 2 years of age)
- •0.8 mg/dL (2 to < 6 years of age)
- •1.0 mg/dL (6 to < 10 years of age)
- •1.2 mg/dL (10 to < 13 years of age)
- •1.5 (male) or 1.4 (female) (13 to < 16 years of age)
- •1.7 (male) or 1.4 (female) ( ≥ 16 years of age)
- •Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit ofnormal
- •ALT ≤ 110 U/L
- •Serum albumin ≥ 2 g/dL
- •QTc interval ≤ 450 milliseconds
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Must be able to swallow capsules or liquids
- •Able to comply withthe safety-monitoring requirements of the study, in the opinion of the investigator
- •No peripheral neuropathy ≥ grade 2 within the past 14 days
- •No known hypersensitivity to vorinostat or bortezomib
- •No uncontrolled infection
- •No concurrent enzyme-inducing anticonvulsants
- •Must be recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
- •More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
- •At least 7 days since prior therapy with any of the following:
- •Hematopoietic growth factors
- •Biologic (anti-neoplastic) agent
- •For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
- •Corticosteroids unless on a stable or decreasing dose
- •At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal antibodies
- •At least 2 weeks since prior local palliative radiotherapy (small port)
- •At least 6 months since prior total-body irradiation therapy, craniospinal radiotherapy, or ≥ 50% of pelvis irradiated
- •At least 6 weeks since prior substantial bone marrow radiotherapy
- •At least 3 months since prior stem cell transplantation or rescue and no evidence of active graft-vs-host disease
- •At least 2 weeks since prior and no concurrent valproic acid
- •At least 6 weeks since priorimmunotherapy (e.g., tumor vaccines)
- 另有 2 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (vorinostat, bortezomib)
Patients receive oral vorinostat once daily on days 1-5 and 8-12 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Treatment (vorinostat, bortezomib)
Patients receive oral vorinostat once daily on days 1-5 and 8-12 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
Treatment (vorinostat, bortezomib)
Patients receive oral vorinostat once daily on days 1-5 and 8-12 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (vorinostat, bortezomib)
Patients receive oral vorinostat once daily on days 1-5 and 8-12 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (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 according to NCI CTCAE version 3.0
时间窗: 21 days
In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.
次要结局
- Disease response assessed according to RECIST criteria(Up to 30 days)