Newly diagnosed with an intracranial or spinal ependymoma (all WHO grades) including ependymoma variants: cellular, papillary, myxopapillary, clear-cell and tanycytic) or anaplastic ependymoma. MedDRA version: 20.0 Level: PT Classification code 10014967 Term: Ependymoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Vincristine
Product Code: VCR
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: VINCRISTINE
CAS Number: 57-22-7
Current Sponsor code: VCR
Concentration unit
Sponsors
Centre Leon Berard
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: OVERALL PROGRAM (staging phase): - Main residence in one of the participating countries - Age 12 months and 12 months and < 22 years at time of study entry, - Residual non reoperable measurable ependymoma based on central neuro-radiological Review (details see protocol) - No metastasis on spinal MRI and on CSF cytology assessments (see section Mandatory Lumbar puncture) -- Post-menarchal female not pregnant or nursing (breast feeding) and with a negative beta-HCG pregnancy test prior to commencing the trial - Males and females
Exclusion criteria
Exclusion criteria: OVERALL PROGRAM - Patient with subependymomas and ependymoblastomas - Primary diagnosis predating the activation of the SIOP Ependymoma II program (Apr 29th 2015) STRATUM 1: - Tumour entity other than primary intracranial ependymoma, - Patients with WHO grade I ependymoma including myxopapillary variant, - Patients with spinal cord location of the primary tumour - Participation within a different trial for treatment of ependymoma - Concurrent treatment with any anti-tumour agents - Inability to tolerate chemotherapy - Unable to tolerate intravenous hydration, - Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results in the judgment of the investigator - Pre-existing mucositis, peptic ulcer, inflammatory bowel disease, ascites, or pleural effusion, - Contraindication to one of the IMP used in the stratum 1 according to the SmPCs in appendix 4 of this protocol (SmPCs in appendix are those from UK which were chosen for the assessment of the safety aspects of the study) - Patient for whom imaging remains RX despite all effort to clarify the MRI conclusion STRATUM 2: - Tumour entity other than primary intracranial ependymoma, - Patients with WHO grade I ependymoma including myxopapillary variant - Patients with spinal cord location of the primary tumour - Participation within a different trial for treatment of ependymoma - Concurrent treatment with any anti-tumour agents - Inability to tolerate chemotherapy - Unable to tolerate intravenous hydration - Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that may increase the risk associated with study participation or investigational productadministration, or may interfere with the interpretation of study results in the judgment of the investigator - Pre-existing mucositis, peptic ulcer, inflammatory bowel disease, ascites, or pleural effusion - Contraindication to one of the IMP used in the stratum 2 according to the SmPCs in appendix 4 of this protocol (SmPCs in appendix are those from UK which were chosen for the assessment of the safety aspects of the study) - Patient for whom imaging remains RX despite all effort to clarify the MRI conclusion STRATUM 3: - Tumour entity other than primary intracranial ependymoma, - Patients with WHO grade I ependymoma including myxopapillary variant - Patients with spinal cord location of the primary tumour - Participation within a different trial for treatment of ependymoma - Concurrent treatment with any anti-tumour agents - Inability to tolerate chemotherapy - Unable to tolerate intravenous hydration - Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results in the judgment of the investigator - Pre-existing mucositis, peptic ulcer, inflammatory bowel disease, ascites, or pleural effusion - Pre-existing severe hepatic and/or renal damage - Family history of severe epilepsy in immediate family siblings - Presence of previously undiagnosed mitochondrial disorder detected by screening as part of trial - Elevated blood ammonium level = 1.5 x upper limit of the normal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Overall program To determine whether the assessment of residual disease can be improved by a centralized review of post-operative MRI and whether such review increases the rate of complete resection compared to historical controls. Does central neurosurgical and radiological review increase resection rates? •Stratum 1 To compare PFS in patients who receive 16 weeks chemotherapy with VEC+CDDP following complete surgical resection, with no residual disease, and radiotherapy when compared to those that undergo complete surgical resection, with no residual disease, and radiotherapy alone. •Stratum 2 To compare the activity of 2 post-operative chemotherapy schedules with VEC or VEC+HD-MTX in patients who have incompletely resected tumour. •Stratum3 To evaluate the PFS in children unable to receive radiation therapy and who receive valproate, as a HDCAI in addition to the primary chemotherapy strategy when compared to those that undergo chemotherapy without valproate. ;Secondary Objective: •Overall program To evaluate second look surgery rates as compared to historical controls •Stratum 1 To evaluate whether OS is improved To compare the neuroendocrine morbidity To evaluate the QoS To evaluate the neurophychological morbidity To determine the safety and tolerance •Stratum 2 To determine the safety and tolerability To evaluate whether OS is improved To evaluate whether PFS is improved To compare neuroendocrine morbidity To evaluate the QOS To evaluate the neuropsychological morbidity To determine Safety of 8 Gy Boost radiotherapy •Stratum 3 To evaluate whether OS is improved To evaluate whether radiotherapy free survival is improved To compare the neuroendocrine morbidity To evaluate the Quality of Survival To evaluate the neuropsychologica morbidity To determine the safety and tolerability of valproate;Primary end point(s): Overall program: Gross Total Resection (GTR) rate (Only descriptive statistics will be produced) Stratum 1 Progress | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall program: Second look surgery rate (Only descriptive statistics will be produced) •Startum 1: Overall survival measured from the date of randomisation to the date of death due to any cause. Quality of survival (QoS) Neuropsychological outcomes Neuroendocrine outcomes (Neuroendocrine late effects) Short and long term Safety: Adverse Events (CTCAE v4.03) •Stratum 2: Overall survival measured from the date of randomisation to the date of death due to any cause. Progression Free Survival from the date of randomisation to the date of event defined as progression or death due to any cause. Quality of survival (QoS) Neuropsychological outcomes Neuroendocrine outcomes (Neuroendocrine late effects) Short and long term safety of frontline chemotherapy: Adverse Events (CTCAE v4.03) Exploratory endpoint measure: Toxicity will be monitored in the subgroup receiving radiotherapy boost. Event Free survival for patients with boost of radiotherapy. •Stratum 3: Overall survival measured from the date of randomisation to the date of death due to any cause. Radiotherapy free survival rate Quality of survival (QoS) Neuropsychological outcomes Neuroendocrine outcomes (Neuroendocrine late effects) Short and long term Safety and Toxicity of frontline chemotherapy based on proportion of patients experiencing Toxicity grade 3 to 4 (Adverse Events (CTCAE v4.03)). Exploratory Endpoint measures (optional): Pharmacokinetic modelling will be carried out using Valproate pharmacokinetic parameters in conjunction with patient characteristics and clinical parameters in order to investigate the key factors involved in determining individual valproate drug exposures within the patient population. •Valproate pharmacodynamics will be followed throughout changes in histone H3 and H4 acetylation. Changes between baseline and time of steady state valproate will be correlated with valproate trough levels and clinical response. ;Timepoint( | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Finland, Germany, Ireland, Italy, Netherlands, Norway, Spain, Sweden
Contacts
Public ContactDRCI- Pôle opérations cliniques
CENTRE LEON BERARD
Outcome results
None listed