Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma
Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma
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
Secondary objectives
INCLUSION CRITERIA:
Participant must have recurrent or refractory intracranial or spinal ependymoma (including myxopapillary, clear cell, papillary, tanycytic and anaplastic ependymoma or subependymoma). The diagnosis must be confirmed by the pathologist on tissue obtained at either initial diagnosis or at time of recurrence prior to registration.
Participants may have had two prior systemic anti-cancer chemotherapy regimens, including any chemotherapy, biologic modifiers or small molecules. These may have been given either before or after irradiation.
Participant must be < 22 years (eligible until 22nd birthday) of age at the time of enrollment.
Negative testing for DPYD*2 any time prior to enrollment (does not need to be within 7 days)
Neurologic deficits: Participants with neurological deficits should have a stable or improving neurologic exam for a minimum of 1 week prior to study registration.
Performance level: Karnofsky Performance Scale (participants > 16 years of age) or Lansky Performance Score (participants ≤ 16 years of age) must be > 30 within two weeks prior to registration.
Chemotherapy: Participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least four weeks prior to study registration or at least six weeks if nitrosurea. At least two weeks must have lapsed if participants received lower dose oral etoposide (50 mg/m^2) without experiencing evidence of myelosuppression (i.e., neutropenia or requiring transfusion with blood products).
Biologic agent: Participant must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration. For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the PI prior to registration.
Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration. Such participants should be discussed with the PI prior to registration
XRT: No more than two prior radiation regimens. For participants who have had prior irradiation for treatment of their ependymoma. XRT must be:
Bone marrow or stem cell transplant: Participant must be ≥ 3 months since high dose chemotherapy and peripheral blood stem cell rescue prior to registration
Anti-convulsants: Participants with seizure disorder may be enrolled if well controlled on anti-epileptic drugs.
Corticosteroids: Participants who are taking corticosteroids must be on a stable or decreasing dose for at least 1 week prior to registration.
Growth factors: Participants must be off all colony forming growth factors(s) for at least 1 week prior to registration (e.g. filgrastim, sargramostim, erythropoietin) and at least 2 weeks for long-acting formulations (e.g. Neupogen®).
Adequate organ function at the time of study enrollment as defined as follows: Laboratory values must be assessed within 7 days prior to registration and must be repeated if initial labs were done greater than 7 calendar days prior to the start of therapy:
EXCLUSION CRITERIA: