A Feasibility Study of Vorinostat (SAHA) Combined With Isotretinoin and Chemotherapy in Infants With Embryonal Tumors of the Central Nervous System
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 15
- 主要终点
- Feasibility in terms of completing 3 courses of induction therapy
研究概览
简要总结
This pilot clinical trial studies the side effects and the best way to give vorinostat with isotretinoin and combination chemotherapy and to see how well they work in treating younger patients with embryonal tumors of the central nervous system. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as isotretinoin, vincristine sulfate, cisplatin, cyclophosphamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vorinostat with isotretinoin and combination chemotherapy may be an effective treatment for embryonal tumors of the central nervous system. A peripheral blood stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed.
详细描述
PRIMARY OBJECTIVES:
I. To investigate the feasibility of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.
II. To describe the toxicity of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.
III. To investigate prognostic values of histopathological classification and biological markers in the context of a feasibility study.
SECONDARY OBJECTIVES:
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
- 2 Months 至 47 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a histologically confirmed, newly-diagnosed medulloblastoma (except for patients with the histology of localized (M0) desmoplastic medulloblastoma or atypical teratoid/rhabdoid tumor [ATRT]) or supratentorial primitive neuroectodermal tumor (PNET) including pineoblastomas
- •Patients must have not received any prior therapy other than surgery and/or steroids
- •Patient must have adequate pre-trial formalin-fixed, paraffin-embedded (FFPE) tumor material available for use in the biology studies and central pathology review; if snap frozen tissue is not available, the study chair must be contacted to discuss eligibility
- •Patient must be a suitable candidate, by institutional standards for stem cell apheresis
- •Lansky performance score (LPS for =< 16 years of age) >= 30 assessed within two weeks prior to registration
- •Absolute neutrophil count (ANC) >= 1000/ul (unsupported) (within 14 days of registration and within 7 days of the start of treatment)
- •Platelets >= 100,000/ul (unsupported) (within 14 days of registration and within 7 days of the start of treatment)
- •Hemoglobin >= 8 g/dL (may be supported) (within 14 days of registration and within 7 days of the start of treatment)
- •Bilirubin < 1.5 times upper limit of normal for age (within 14 days of registration and within 7 days of the start of treatment)
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 times institutional upper limit of normal for age (within 14 days of registration and within 7 days of the start of treatment)
- •Serum creatinine =< 1.5 times upper limit of institutional normal for age or glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or estimated GFR (Schwartz bedside) that is > 99 ml/min/1.73 m^2 (within 14 days of registration and within 7 days of the start of treatment)
- •Parents/legal guardians must have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines
排除标准
- •Patients with diagnosis of atypical teratoid/rhabdoid tumor (ATRT by histology, immunohistochemistry and/or molecular analysis) and desmoplastic M0 medulloblastoma will be excluded from the study
- •Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would interfere with the study procedures or results
- •Patients receiving any other anticancer or investigational drug therapy are excluded
- •Patients having taken valproic acid within 2 weeks prior to initiation of treatment are excluded
- •Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
- •Patients with a parabens allergy
研究组 & 干预措施
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Carboplatin (Drug)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Cisplatin (Drug)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Etoposide Phosphate (Drug)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Isotretinoin (Drug)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Thiotepa (Drug)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
Treatment (vorinostat, isotretinoin, chemotherapy)
See Detailed Description
干预措施: Vorinostat (Drug)
结局指标
主要结局
Feasibility in terms of completing 3 courses of induction therapy
时间窗: Within 98 days
Simon's two-stage optimal design will be used to assess feasibility.
Dose-limiting toxicity of proposed vorinostat
时间窗: Up to 21 days
Will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Prognostic value of histopathological classification of pediatric medulloblastoma
时间窗: Up to 5 years
Will be assessed by single-nucleotide polymorphism (SNP) analysis and gene expression analysis. Loss of heterozygosity (LOH) analysis and copy number analysis (CNA) will be performed using dChip SNP software (or R bioconductor package) for the paired samples. Association of copy number (and LOH) with gene expression data will be explored. Correlation analysis (Pearson or Spearman Correlation, as appropriate) will be used to estimate the strength of association between each SNP and expression signal. The multiplicity issue will be addressed through estimating the False Discovery Rate.
次要结局
- Predictive values of biological markers in CSF, plasma and urine in the context of a feasibility study(Up to 5 years)
- Response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites)(Up to 5 years)
- Progression-free survival (PFS)(Up to 5 years)
- Overall survival (OS)(Up to 5 years)