NCT02630043终止1 期
A Phase I Trial of Tolcapone Alone and in Combination With Oxaliplatin in Patients With Relapsed or Refractory Neuroblastoma
Giselle Sholler9 个研究点 分布在 1 个国家目标入组 5 人开始时间: 2015年12月最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 9
- 主要终点
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
The purpose of this research study is to evaluate an investigational drug (Tolcapone) alone and in combination with oxaliplatin, for relapsed and refractory neuroblastoma. Tolcapone is approved by the U.S. Food and Drug Administration (FDA) for adults, but is an investigational drug in this study because it has not been approved in pediatrics for this indication. Oxaliplatin, although a drug approved by the FDA for other cancers, is investigational for treatment of neuroblastoma in this study. This study will look at the safety and tolerability of tolcapone in combination with oxaliplatin as well as the tumors response to this study drug.
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
- 0 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: ≤ 21 years at the time of study entry.
- •Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
- •Disease Status: Patients must have ONE of the following:
- •Any episode of recurrent disease following completion of aggressive multi-drug frontline therapy.
- •Any episode of progressive disease during aggressive multi-drug frontline therapy.
- •Primary resistant/refractory disease detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocols.
- •Measurable or evaluable disease, including at least one of the following: measureable tumor by CT or MRI; a positive MIBG, or PET scan; positive bone marrow biopsy/aspirate.
- •Current disease state must be one for which there is currently no known curative therapy
- •A negative urine or serum pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
- •Organ Function Requirements:
- •Subjects must have adequate liver function as defined by:
- •AST and ALT ≤ upper limit of normal
- •Serum bilirubin must be ≤ 2.0 mg/dl
- •Subjects must have adequate Bone Marrow function defined as:
- •For patients without bone marrow involvement:
- •Peripheral absolute neutrophil count (ANC) >750/uL
- •Subjects must have adequate renal function
- •Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for 90 days after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
- •Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.
排除标准
- •Lansky score <50%
- •BSA (m2) of <0.5
- •Prior Therapy- Patients must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
- •Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
- •Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
- •Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic 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. The duration of this interval must be discussed with the Study Chair.
- •Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
- •Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody.
- •XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
- •Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 2 months must have elapsed since transplant.
- •Investigational Drugs: Subjects who have received another investigational drug within the last 14 days are excluded from participation.
- •Subjects with CNS lesions are excluded
- •Subjects with a history of depression, anxiety, or psychotic disorders (due to tolcapone adverse event profile).
- •Subjects that are pregnant or breastfeeding an infant.
- •Subjects that cannot swallow tablets.
- •Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
- •Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
研究组 & 干预措施
Tolcapone and Oxaliplatin
Experimental
Subjects will receive oral tolcapone at their assigned dose level on each day of this 21-day cycle.
Oxaliplatin will be given at 100 mg/m2 IV on Day 1 of Cycle 2 through 5 and any subsequent 21-day cycle.
干预措施: Tolcapone (Drug)
Tolcapone and Oxaliplatin
Experimental
Subjects will receive oral tolcapone at their assigned dose level on each day of this 21-day cycle.
Oxaliplatin will be given at 100 mg/m2 IV on Day 1 of Cycle 2 through 5 and any subsequent 21-day cycle.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
时间窗: 2 years
To determine the safety and tolerability of tolcapone alone and in combination with oxaliplatin at 4 dose levels of tolcapone
次要结局
- Determine the Progression Free Survival (PFS) of Participants using days until progression(3 years)
- To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Plasma clearance (Cl).(24 hours)
- To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Peak Plasma Concentration (Cmax)(24 hours)
- Determine the Overall Response Rate (ORR) of Participants using RECIST criteria(3 years)
- To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Plasma half-life (t1/2).(24 hours)
- To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Vd.(24 hours)
- To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Area Under the Curve (AUC).(24 hours)
研究者
Giselle Sholler
Study Chair
Milton S. Hershey Medical Center
研究点 (9)
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