NCT02395666已完成2 期
A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission
Giselle Sholler22 个研究点 分布在 1 个国家目标入组 140 人开始时间: 2015年3月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 140
- 试验地点
- 22
- 主要终点
- Number of Participants With Event Free Survival (EFS) During Study.
研究概览
简要总结
The purpose of this research study is to evaluate a new investigational drug to prevent reoccurrence of neuroblastoma that is in remission. This study drug is called DFMO. The objectives of this study will be to monitor for safety and 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 may continue on treatment up to 27 cycles 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), meta-iodobenzylguanidine (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.
The proposed dosing regimen is an oral dose of DFMO tablets two times a day for each day while on study. There will be 27 cycles. Each cycle will be 28 days in length.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 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 a previous relapse of high risk neuroblastoma.
- •Disease Status: Neuroblastoma that is in remission
- •First dose of study medication must be greater than 30 days from completion of cytotoxic and antibody therapy and less than 120 days from previous therapy
- •A negative serum or urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
- •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 six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrel implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
- •Absolute Neutrophil Count (ANC) > 500/μl and platelet count >50,000/μl
- •Organ Function Requirements: Subjects must have adequate liver function as defined by:
- •Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) <10x upper limit of normal
- •Serum bilirubin must be ≤ 2.0 mg/dl
- •Serum creatinine based on age/gender
- •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 < 60%
- •Body Surface Area (BSA) (m2) of <0.25
- •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 twice daily
Experimental
Subjects will receive twenty-seven (27) cycles of oral DFMO at a dose of 500 to 1000 mg/m2 BID on each day of a 28 day cycle.
干预措施: DFMO (Drug)
结局指标
主要结局
Number of Participants With Event Free Survival (EFS) During Study.
时间窗: 2 Years
To evaluate the preventative activity of DFMO as a single agent in patients that are in remission based on: Event free survival (EFS)
次要结局
- Test the Association of Survival With ODC1 Genotype(2 years)
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(2 years)
- Percentage of Participants With Overall Survival (OS)(2 Years)
- Area Under the Plasma Concentration Versus Time Curve (AUC)(0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days)
- Time to Reach Peak Plasma Concentration (Tmax)(0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days)
- Peak Plasma Concentration (Cmax)(Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days)
研究者
Giselle Sholler
Beat Childhood Cancer Chair
Milton S. Hershey Medical Center
研究点 (22)
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相关资讯
Norgine Seeks EMA Approval for Eflornithine in High-Risk Neuroblastoma• Norgine has submitted a marketing authorization application to the EMA for eflornithine to treat high-risk neuroblastoma (HRNB).
• The application follows prior submissions in Australia, Switzerland, and the United Kingdom under Project Orbis.
• Eflornithine is intended as an oral maintenance therapy to reduce relapse risk in pediatric and adult HRNB patients.
• FDA approved eflornithine in December 2023 based on trials showing improved event-free and overall survival.last yearNorgine Seeks Approval for Eflornithine in High-Risk Neuroblastoma via Project Orbis- Norgine B.V. has submitted marketing authorization applications for eflornithine in Australia, Switzerland, and the United Kingdom for high-risk neuroblastoma (HRNB).
- The submissions are part of Project Orbis, an initiative to expedite the approval of innovative oncology products across multiple countries.
- Eflornithine is intended as an oral maintenance therapy to reduce the risk of relapse in pediatric and adult patients with HRNB.
- FDA approved eflornithine in December 2023 based on trials showing improved event-free and overall survival compared to standard of care.2 years agoEflornithine Approved for High-Risk Neuroblastoma: EMA Approval Still Pending- Eflornithine (Iwilfin) is FDA-approved for high-risk neuroblastoma in adults and children who have shown a partial response to prior therapies, including anti-GD2 immunotherapy.
- Clinical trials demonstrated that eflornithine reduces the risk of relapse, with a hazard ratio for event-free survival of 0.48 and a hazard ratio for overall survival of 0.32.
- As of March 2024, there is no active application for eflornithine's EMA approval, making its availability in Europe unlikely in the near future.
- Patients in Europe may potentially access eflornithine through clinical trials or via Named Patient Import regulations, requiring a prescription from their doctor.2 years agoEflornithine Approved by FDA for High-Risk Neuroblastoma to Reduce Relapse Risk• The FDA has approved eflornithine (Iwilfin) to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB).
• The approval is for patients who have achieved at least a partial response to prior multi-agent, multimodality therapy, including anti-GD2 immunotherapy.
• Efficacy was demonstrated in an externally controlled trial, showing a significant improvement in event-free survival (EFS) and overall survival (OS).
• Common adverse effects included otitis media, diarrhea, cough, and hearing loss, but the drug's manageable safety profile supported its approval.2 years agoFDA Panel Supports Eflornithine for High-Risk Pediatric Neuroblastoma• The FDA's Oncologic Drugs Advisory Committee (ODAC) voted 14-6 in favor of eflornithine to reduce relapse risk in pediatric high-risk neuroblastoma patients.
• The vote was based on data from Study 3b, a single-arm trial with an external control arm from the ANBL0032 trial, showing improved event-free survival.
• Eflornithine's safety profile includes manageable toxicities like hearing loss, with dose adjustments potentially mitigating adverse effects.
• While some panel members expressed concerns about using an externally controlled trial, the overall consensus was that the benefits outweigh the risks.2 years ago