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


Phase 1
1 Month
21 Years
Open (Enrolling)
Both
Central Nervous System Malignancies, Ependymoma

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Trial Information

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


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

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

Inclusion Criteria


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 any number of prior systemic anti-cancer treatment 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: 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
Gy)

- ≥ 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 as shown below or GFR
> 70ml/min/1.73m^2

- If age is 1 month to < 6 months: maximum serum creatinine is 0.4 mg/dL in
males and females

- If age is 6 months to < 1 year: maximum serum creatinine is 0.5 mg/dL in
males and females

- If age is 1to < 2 years: maximum serum creatinine is 0.6 mg/dL in males
and females

- If age is 2 to < 6 years: maximum serum creatinine is 0.8 mg/dL in males
and females

- If age is 6 to < 10 years: maximum serum creatinine is 1 mg/dL in males
and females

- If age is 10 to < 13 years: maximum serum creatinine is 1.2 mg/dL in males
and females

- If age is 13 to < 16 years: maximum serum creatinine is 1.5 mg/dL in males
and 1.4 mg/dL in females

- If age is > or = 16 years: maximum serum creatinine is 1.7 mg/dL in males
and 1.4 mg/dL in females

- 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
method.

- Participants must not breastfeed while on this study

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

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

Outcome Description:

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

Outcome Time Frame:

At the end of the 6-week dose limiting toxicity observation period.

Safety Issue:

Yes

Principal Investigator

Karen D. Wright, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Jude Children's Research Hospital

Authority:

United States: Institutional Review Board

Study ID:

SJREFU

NCT ID:

NCT01498783

Start Date:

December 2011

Completion Date:

December 2017

Related Keywords:

  • Central Nervous System Malignancies
  • Ependymoma
  • Neoplasms
  • Ependymoma

Name

Location

St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794