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Central Nervous System MalignanciesPhase 1SJREFUNCT01498783

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

A Phase 1 study testing 5-fluorouracil in people with Central Nervous System Malignancies and Ependymoma, run by St. Jude Children's Research Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 month to 21 years
What is being tested?
5-fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
Dec 2011to May 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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 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 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

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.

Read the 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
Being tested
5-fluorouracil
Medical subject headings
Ependymoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5-fluorouracilDrug

    Also called 5-FU

    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).

Study groups in NCT01498783
Study groupRoleWhat they receive
TreatmentExperimentalParticipants meeting the eligibility requirements. Intervention: 5-fluorouracil
Receives: Drug: 5-fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

    Measured: Pharmacokinetics on day 1, day 8, and day 22 of course 1, and day 1 of course 2

  3. 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.

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

Secondary outcomes (4)

  1. Descriptive report of toxicities.

    To document and describe toxicities associated with 5-FU administered on a weekly bolus schedule

    Measured: Throughout treatment, up to two years per patient

  2. Tumor response and progression-free survival

    To document preliminary antitumor activity in participants with recurrent or refractory ependymoma treated with 5-FU

    Measured: at the completion of therapy (2 years)

  3. 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

    Measured: At the end of accrual (3 years)

  4. 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

    Measured: At the end of therapy (2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionMay 2014
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01498783
Sponsor's protocol ID
SJREFU
Other IDs
NCI-2012-00368
Acronym
SJREFU
Status last verified
Jul 2015
First submitted
21 Dec 2011
Last updated
2 Feb 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 5-fluorouracil in people with Central Nervous System Malignancies and Ependymoma, run by St. Jude Children's Research Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimate the maximum tolerated dose determined using the Rolling 6 design using the CTCAEv4 to assess DLT. (time frame: At the end of the 6-week dose limiting toxicity observation period.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01498783.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2016.

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