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Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma

Information source: St. Jude Children's Research Hospital
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Central Nervous System Malignancies; Ependymoma

Intervention: 5-fluorouracil (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: St. Jude Children's Research Hospital

Official(s) and/or principal investigator(s):
Karen D. Wright, MD, Principal Investigator, Affiliation: St. Jude Children's Research Hospital


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.

Clinical Details

Official title: Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Estimate the maximum tolerated dose determined using the Rolling 6 design using the CTCAEv4 to assess DLT.

Pharmacokinetic modeling of 5-fluorouracil concentrations

Estimate the maximum tolerated dose in less heavily pre-treated children

Secondary outcome:

Descriptive report of toxicities.

Tumor response and progression-free survival

Expression level of TYMS in FFPE tumor samples

Description of association between genetic polymorphism and pharmacokinetics

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


- 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


Minimum age: 1 Month. Maximum age: 21 Years. Gender(s): Both.



- 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


- 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:

- ≥ 6 months prior to registration if treated with craniospinal irradiation (≥ 18


- ≥ 4 weeks prior to registration if treated with focal irradiation to the

primary tumor

- ≥ 2 weeks prior to registration if treated with focal irradiation to symptomatic

metastatic sites

- 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:

- Bone marrow: Absolute neutrophil count (ANC) ≥ 500/μL, platelet count ≥

50,000/μL (transfusion independent), hemoglobin concentration ≥ 8g/dL (may be transfused)

- Renal: Normal serum creatinine concentration based on age or GFR >

70ml/min/1. 73m^2

- Hepatic: Total bilirubin concentration < 1. 5x the institutional upper limit of

normal for age; SGPT and SGOT < 2. 5 x the institutional upper limit of normal EXCLUSION CRITERIA:

- Participants may not have been previously treated with 5-FU

- Participants receiving any other anticancer or experimental treatment

- Participants with uncontrolled infection

- Participants with any concomitant significant medical illness that in the

investigator's opinion cannot be adequately controlled with appropriate therapy, or that would compromise the participant's ability to tolerate therapy, impair the evaluation of side effects related to this treatment, or alter drug metabolism

- Females of childbearing potential must have a negative serum or urine pregnancy test

within 7 days prior to study entry.

- Participants of child bearing potential must agree to use an effective contraceptive


- Participants must not breastfeed while on this study

Locations and Contacts

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Additional Information

St. Jude Children's Research Hospital

Clinical Trials Open at St. Jude

Starting date: December 2011
Last updated: July 24, 2015

Page last updated: August 20, 2015

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