NCT00513162已完成1 期
Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Individual Maximal Tolerated Doses (iMTD)
研究概览
简要总结
Primary Objective:
- Determine the interindividual range and median of individual maximum tolerated doses of valproic acid administered as one time evening dose in conjunction with a dose oral etoposide (50 mg/m2/day for children, but only 25mg/m2/day for adults to start) for four different age groups.
Secondary Objectives:
- Determine the qualitative and quantitative toxicity and reversibility of toxicity of valproic acid in conjunction with oral etoposide,
- To investigate the clinical pharmacokinetics of valproic acid when given in conjunction with oral etoposide,
- To describe quality of life of patients with relapsed, or progressive central and peripheral nervous system tumors when treated with oral valproic acid and etoposide,
- To observe and describe the response pattern of progressive central nervous system tumors treated with oral valproic acid and etoposide,
- To observe and describe event free survival time and overall survival time of patients with relapsed, or progressive central nervous system tumors when treated with oral valproic acid and etoposide,
- To determine if histone deacetylase activity and topoisomerase expression in lymphocytes of patients is related to valproic acid levels, and
- To determine, if the individual maximal tolerated dose (iMTD) depends on the initial performance status of the patient in the beginning of the treatment.
详细描述
Study Drugs:
Etoposide is designed to block cell growth by breaking the DNA, which may cause the cells to die.
Valproic acid was first designed as an anti-seizure medication. It was also found to change cancer cells and make them more sensitive to etoposide.
Screening Tests:
Before you start treatment on this study, you will have "screening tests". These tests help your doctor decide if you are eligible to take part in this 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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diseases: Diagnosis of a neuroectodermal tumor of the central or peripheral nervous system or a brain metastasis.
- •Disease confirmation: Patients must have a diagnosis of a malignant tumor proven by the diagnostic method considered standard of care for the specific tumor.
- •Disease progression and treatment failure: Patient must have failed standard front-line treatment and must not be eligible for any higher-priority therapy.
- •Negative pregnancy test for female patients between menarche and menopause is required.
- •Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
- •Approval for the use of this treatment regimen by the individual's Human Rights Committee or Institutional Review Board (IRB) must be obtained in accordance with the individual institutional policies and the local, state, and national rules, regulations and laws, is mandatory for an enrolling institution. The documentation of this approval must be on file at the MDAnderson Cancer Center Pediatric Oncology Trials Office prior to enrollment of any patient on study.
排除标准
- •Neurofibromatosis type I.
- •Known or suspected inborn errors of metabolism.
- •Patients who require any of the following medications are excluded from enrollment: Carbamazepine, Oxcarbazepine, Primidone, Phenobarbital, Topiramate, Carbapenem antibiotics (ertapenem, imipenem, meropenem), Felbamate, Isoniazid, Lamotrigine, Macrolide antibiotics (clarithromycin, erythromycin, troleandomycin, azithromycin), Zidovudine, Risperidone, Salicylates.
- •Patients who take antiviral medications usually targeted to treat HIV infections or have clinical signs for acquired immunodeficiency syndrome (AIDS) are excluded. HIV testing is not mandatory.
- •Patients who had previous chemotherapy less than three weeks (21 days) ago cannot be enrolled: Patients must have been off all previous chemotherapy or radiotherapy for the 3 weeks prior to initiation of study treatment and recovered from toxic effects of that therapy.
- •Patients which are on a stable dose for valproic acid prior to enrolment are not eligible.
- •Patients which have been treated with valproic acid or other histone deacetylase inhibitors such as SAHAa or MS275 and the treatment has failed to control the tumor are not eligible.
- •Patient which have been treated with oral continuous etoposide previously and the treatment has failed to control the tumor are not eligible.
- •White blood cell count below 2,000/µL excludes patient from enrollment.
- •Absolute neutrophil count below 700/uL excludes patient from enrollment.
- •Platelet count below 80,000 excludes patient from enrollment.
- •Pancreatitis with amylase above two times the upper normal limit excludes patient from enrollment, (even in the absence of clinical signs of pancreatitis).
- •Somnolence at daytime for more than 6 hours excludes patient from enrollment
- •Bilirubin total > 1.5 mg/dL excludes patient from enrollment.
- •ALT > 2.5 times upper normal value excludes patient from enrollment.
- •AST >2.5 x upper normal value excludes patients from enrollment.
- •Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction) excludes patient from enrollment.
- •Pregnant or nursing women cannot be enrolled.
- •Women of childbearing potential who are not using an effective method of contraception cannot be enrolled.
研究组 & 干预措施
Valproate + Etoposide
Experimental
Valproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m^2 By Mouth Daily.
干预措施: Valproate (Drug)
Valproate + Etoposide
Experimental
Valproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m^2 By Mouth Daily.
干预措施: Etoposide (Drug)
结局指标
主要结局
Individual Maximal Tolerated Doses (iMTD)
时间窗: Continuous assessment and determination of dose-limiting toxicities with each dose level (increasing dose weekly)
次要结局
未报告次要终点
研究者
研究点 (1)
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