Recurrent or refractory ependymoma MedDRA version: 17.1 Level: PT Classification code 10014967 Term: Ependymoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: 5-fluorouracil
Product Name: Fluorouracil
Product Code: Not applicable
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Fluorouracil
CAS Number: 51-21-8
Current Sp
Sponsors
Royal Marsden NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients aged 1-24 years old at the time of informed consent. - Histological confirmation of ependymoma at the time of initial diagnosis. - Relapsed or progressed disease following previous standard treatment including radiotherapy. N.B.: patients suitable for re-irradiation at the time of relapse might still be eligible for the present study. - Stable neurologic examination. - Measurable disease as per RECIST 1.1. - Life expectancy of = 12 weeks. - Performance status as follows: Lansky scale = 50% for patients =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - The patient must not have received, at the time of eligibility assessment: o any myelosuppressive chemotherapy within 3 weeks (exceptions: 6 weeks if prior nitrosourea, or 1 week if low dose metronomic chemotherapy); o any biological agent within 2 weeks; o focal radiotherapy within 4 weeks or craniospinal radiotherapy within 3 months; o any investigational therapy within 4 weeks. Investigational therapy is defined as any medicinal product that is not approved in the UK for any indication. - Concomitant use of dehydropyrimidine dehydrogenase (DPD) inhibitors, such as brivudin, sorivudin and analogues within the previous 4 weeks. - Patients who have an uncontrolled infection. - Known active viral hepatitis, including Hepatitis A, B or C, or known diagnosis of human immunodeficiency virus (HIV) infection. Viral testing is not mandatory. - Pregnant or lactating females. - Low probability of treatment compliance. - Other severe, acute or chronic, medical or psychiatric condition, or laboratory abnormality, that may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: If 5-fluorouracil, given as a bolus followed by continuous infusion over 2 days, can reduce tumour burden in children and young adults with recurrent/refractory ependymoma.;Secondary Objective: If functional MRI can provide objective biomarkers that correlate with clinical outcome.;Primary end point(s): Overall response rate, complete (CR) or partial (PR), after 6 cycles of fluorouracil as per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.;Timepoint(s) of evaluation of this end point: At baseline and after 6 cycles of chemotherapy (i.e. 12 weeks). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Evaluate the safety and tolerability of 5-FU 400 mg/m2 bolus followed by 2,400 mg/m2 in continuous intravenous infusion over 48 hours in children and young adults with relapsed/refractory ependymoma who have received previous radiotherapy. Safety will assessed by the incidence and severity of adverse events (AE) and serious adverse events (SAE), changes in laboratory values, assessments of physical examinations, and vital signs. Incidence and severity of adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Tolerability will be assessed by the incidence of AEs leading to delay or discontinuation of 5-FU. As exploratory endpoints we will also preliminarily correlate the overall response rate(ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) with the functional imaging phenotype of the pendymomas before administration of 5-FU and after 6 courses of 5-FU. The imaging phenotype will be defined by: o T1 and T2 relaxation times (s-1); o R2*air (s-1); o iAUC60 (mMol/sec), Ktrans (min-1), Ve (no unit), Kep (min-1), Vp (no unit); o ADC (mm2/sec), ADClow (mm2/sec), ADChigh (mm2/sec); o and Magnetisation Transfer Ratio (%).;Timepoint(s) of evaluation of this end point: The secondary endpoints of the study (safety and tolerability) will be evaluated as a continuum throughout the study. The exploratory functional MRI parameters will be collected at baseline and after 6 cycles of 5-FU. | — |
Countries
United Kingdom
Contacts
Public ContactCarceller
The Royal Marsden NHS Foundation Trust
Outcome results
None listed