A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 7
- 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 a new investigational drug to treat neuroblastoma. This study drug is called DFMO. The objectives of this study will be to monitor for safety and to find a maximum tolerated dose in this population. A secondary objective will be to look at efficacy of DFMO.
The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO and/or etoposide may continue on treatment with the expectation that there will be an overall clinical benefit.
The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), MIBG scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO, and later combined with an already approved drug, etoposide.
The proposed dosing regimen is an oral dose of DFMO two times a day for each day while on study. There will be 5 cycles. Each cycle will be 21 days in length. The first cycle will be DFMO alone. In the second cycle etoposide will be added in and will be given orally once a day for the first 14 days of each cycle (cycles 2-5).
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
- •Age: 0-21 years at the time of diagnosis.
- •Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
- •Disease Status: Refractory or relapsed neuroblastoma
- •Measurable disease, including at least one of the following:
- •Measurable tumor >10mm by CT or MRI A positive MIBG and abnormal urinary catecholamine levels Positive bone marrow biopsy/aspirate.
- •Current disease state must be one for which there is currently no known curative therapy.
- •A negative urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
- •Patients without bone marrow metastases must have an ANC > 500/μl and platelet count >50,000/μl
- •Organ Function Requirements Subjects must have adequate liver function as defined by AST or ALT <10x normal Serum bilirubin must be ≤ 2.0 mg/dl Serum creatinine must be ≥ 1.5 mg/dl
- •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
- •Life expectancy <2 months or Lansky score <30%
- •Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
- •Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (hematological and bone marrow suppression effects)
- •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
DFMO and Etoposide
干预措施: DFMO (Drug)
DFMO and Etoposide
干预措施: Etoposide (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: length of study plus 30 days
To determine the safety, tolerability and maximum tolerated dose (MTD) of DFMO as a single agent and in combination with etoposide in pediatric and young adult patients with refractory or recurrent neuroblastoma
次要结局
- Progression Free Survival (PFS)(2 years)
- Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.(Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours)
- Number of Patients With an Overall Response Rate (ORR) of PR or CR(1 year)
- Cmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.(Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours)
- AUC of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.(Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours)
研究者
Giselle Sholler
Beat Childhood Cancer Chair
Milton S. Hershey Medical Center