Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma
- Conditions
- Central Nervous System MalignanciesEpendymoma
- Interventions
- Registration Number
- NCT01498783
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief Summary
This is a phase I study to investigate the safety and pharmacokinetics of weekly 5-fluorouracil (5-FU) administered as a bolus dose in children and young adults with recurrent or refractory ependymoma. The results from this study will inform a subsequent phase II St. Jude investigator-initiated trial.
- Detailed Description
The initial 5-FU dosage will be 500 mg/m\^2 administered on day 1 of course 1. We plan to treat a maximum of 3 cohorts of research participants (dosage levels - 0, 1, and 2) with escalating doses of 5-FU. A cycle is defined as 42 days. The first 6 weeks of therapy will constitute the dose-limiting toxicity (DLT) evaluation period.
Primary objective
* To investigate the safety and pharmacokinetics (plasma and cerebrospinal fluid) of weekly bolus dose 5-FU in children and young adults with recurrent/refractory ependymoma
* To study the safety of 500 mg/m\^2 weekly bolus dose 5-FU in less-heavily pre-treated children and young adults with recurrent/refractory ependymoma.
Secondary objectives
* To document and describe toxicities associated with 5-FU administered on a weekly bolus schedule
* To document preliminary antitumor activity in participants with recurrent or refractory ependymoma treated with 5-FU
* To assess the feasibility of measuring expression level of Thymidylate Synthetase (TYMS) in formalin fixed paraffin embedded (FFPE) tumor samples using the Quantigene assay
* To evaluate the association between specific genetic polymorphisms (e.g., DPYD) and the pharmacokinetics of 5-FU
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment 5-fluorouracil Participants meeting the eligibility requirements. Intervention: 5-fluorouracil
- Primary Outcome Measures
Name Time Method Estimate the maximum tolerated dose determined using the Rolling 6 design using the CTCAEv4 to assess DLT. At the end of the 6-week dose limiting toxicity observation period. To investigate the safety and pharmacokinetics (plasma and cerebrospinal fluid) of weekly bolus dose 5-fluorouracil (5-FU) in children and young adults with recurrent/refractory ependymoma
Pharmacokinetic modeling of 5-fluorouracil concentrations Pharmacokinetics on day 1, day 8, and day 22 of course 1, and day 1 of course 2 To investigate the safety and pharmacokinetics (plasma and cerebrospinal fluid) of weekly bolus dose 5-fluorouracil (5-FU) in children and young adults with recurrent/refractory ependymoma
Estimate the maximum tolerated dose in less heavily pre-treated children At the end of the 6-week dose limiting toxicity observation period. To investigate the safety and pharmacokinetics (plasma and cerebrospinal fluid) of weekly bolus dose 5-fluorouracil (5-FU) in children and young adults with recurrent/refractory ependymoma and in less heavily pre-treated children.
- Secondary Outcome Measures
Name Time Method Tumor response and progression-free survival at the completion of therapy (2 years) To document preliminary antitumor activity in participants with recurrent or refractory ependymoma treated with 5-FU
Descriptive report of toxicities. Throughout treatment, up to two years per patient To document and describe toxicities associated with 5-FU administered on a weekly bolus schedule
Expression level of TYMS in FFPE tumor samples At the end of accrual (3 years) To assess the feasibility of measuring expression level of Thymidylate Synthetase (TYMS) in formalin fixed paraffin embedded (FFPE) tumor samples using the Quantigene assay
Description of association between genetic polymorphism and pharmacokinetics At the end of therapy (2 years) To evaluate the association between specific genetic polymorphisms (e.g., DPYD) and the pharmacokinetics of 5-FU
Trial Locations
- Locations (1)
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States