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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01498783
First received: December 21, 2011
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Central Nervous System Malignancies
Ependymoma
Drug: 5-fluorouracil
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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

  • Pharmacokinetic modeling of 5-fluorouracil concentrations [ Time Frame: Pharmacokinetics on day 1, day 8, and day 22 of course 1, and day 1 of course 2 ] [ Designated as safety issue: No ]
    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

  • Estimate the maximum tolerated dose in less heavily pre-treated children [ Time Frame: At the end of the 6-week dose limiting toxicity observation period. ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Descriptive report of toxicities. [ Time Frame: Throughout treatment, up to two years per patient ] [ Designated as safety issue: Yes ]
    To document and describe toxicities associated with 5-FU administered on a weekly bolus schedule

  • Tumor response and progression-free survival [ Time Frame: at the completion of therapy (2 years) ] [ Designated as safety issue: No ]
    To document preliminary antitumor activity in participants with recurrent or refractory ependymoma treated with 5-FU

  • Expression level of TYMS in FFPE tumor samples [ Time Frame: At the end of accrual (3 years) ] [ Designated as safety issue: No ]
    To assess the feasibility of measuring expression level of Thymidylate Synthetase (TYMS) in formalin fixed paraffin embedded (FFPE) tumor samples using the Quantigene assay

  • Description of association between genetic polymorphism and pharmacokinetics [ Time Frame: At the end of therapy (2 years) ] [ Designated as safety issue: No ]
    To evaluate the association between specific genetic polymorphisms (e.g., DPYD) and the pharmacokinetics of 5-FU


Estimated Enrollment: 27
Study Start Date: December 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

Participants meeting the eligibility requirements.

Intervention: 5-fluorouracil

Drug: 5-fluorouracil
5-fluorouracil, bolus dose of 500 mg/m2 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).
Other Name: 5-FU

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
  Eligibility

Ages Eligible for Study:   1 Month to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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:

    • ≥ 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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498783

Contacts
Contact: Karen D. Wright, MD 866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Karen D. Wright, MD    866-378-5833    info@stjude.org   
Principal Investigator: Karen D. Wright, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Karen D. Wright, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01498783     History of Changes
Other Study ID Numbers: SJREFU
Study First Received: December 21, 2011
Last Updated: February 18, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Ependymoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Fluorouracil
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014