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.
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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
5-fluorouracil, bolus dose of 500 mg/m\^2 given weekly for 4 weeks followed by a two week rest period equals one cycle (6 weeks). Therapy may continue for up to 16 cycles (about 2 years).
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Estimate the maximum tolerated dose determined using the Rolling 6 design using the CTCAEv4 to assess DLT.
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
Time frame: At the end of the 6-week dose limiting toxicity observation period.
Pharmacokinetic modeling of 5-fluorouracil concentrations
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
Time frame: Pharmacokinetics on day 1, day 8, and day 22 of course 1, and day 1 of course 2
Estimate the maximum tolerated dose in less heavily pre-treated children
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.
Time frame: At the end of the 6-week dose limiting toxicity observation period.
Descriptive report of toxicities.
To document and describe toxicities associated with 5-FU administered on a weekly bolus schedule
Time frame: Throughout treatment, up to two years per patient
Tumor response and progression-free survival
To document preliminary antitumor activity in participants with recurrent or refractory ependymoma treated with 5-FU
Time frame: at the completion of therapy (2 years)
Expression level of TYMS in FFPE tumor samples
To assess the feasibility of measuring expression level of Thymidylate Synthetase (TYMS) in formalin fixed paraffin embedded (FFPE) tumor samples using the Quantigene assay
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Time frame: At the end of accrual (3 years)
Description of association between genetic polymorphism and pharmacokinetics
To evaluate the association between specific genetic polymorphisms (e.g., DPYD) and the pharmacokinetics of 5-FU
Time frame: At the end of therapy (2 years)