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

NCT01498783 | Completed Phase 1

• 2 other identifiers: SJREFUNCI-2012-00368
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Central Nervous System Malignancies; Ependymoma

Outcome Measures

Primary Outcomes (3)

• 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

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

• 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

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

• 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.

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

Secondary Outcomes (4)

• Descriptive report of toxicities.

  Throughout treatment, up to two years per patient

• Tumor response and progression-free survival

  at the completion of therapy (2 years)

• Expression level of TYMS in FFPE tumor samples

  At the end of accrual (3 years)

• Description of association between genetic polymorphism and pharmacokinetics

  At the end of therapy (2 years)

Study Arms (1)

Treatment

EXPERIMENTAL

Participants meeting the eligibility requirements. Intervention: 5-fluorouracil

Drug: 5-fluorouracil

Interventions

5-fluorouracil DRUG

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).

Also known as: 5-FU

Treatment

Eligibility Criteria

• Age: 1 Month - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Ependymoma

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinton F. Stewart, PharmD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2011
• First Posted: December 23, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: February 2, 2016

Record last verified: 2015-07

Locations

US (1)