SIOP Ependymoma II - An International Clinical Program for the diagnosis and treatment of children, adolescents and young adults with Ependymoma

Phase 1

• Conditions: ewly diagnosed with an intracranial or spinal ependymoma (all WHO grades) including ependymoma variants: cellular, papillary, myxopapillary, clear-cell and tanicytic) or anaplastic ependymoma.; MedDRA version: 18.1Level: PTClassification code 10014967Term: EpendymomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-002766-39-FI
• Lead Sponsor: CENTRE LEON BERARD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-03-21
• Last Update Posted: 9 May 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

Overall program
• Main residence in one of the participating countries
• Age < 22 years old at the diagnosis
• Newly diagnosed intracranial or spinal ependymoma (all WHO grades) including ependymoma variants: cellular, papillary myxopapillary, clear-cell and tanicytic) or anaplastic ependymoma
• Delivery to national referral pathology center of FFPE tumour tissue blocks (or charged slides with sufficient interpretable material and curls in an Eppendorf tube)
• Written informed consent for data and study biological samples collection
• All patients and/or their parents or legal guardians willing and able to comply with protocol schedule and agree to sign a written informed consent
• Patients must be affiliated to a Social Security System in countries where this is mandatory

After Initial surgery and staging phase, patients will be enrolled in one of 3 different interventional strata where they will be offered a set of therapeutic interventions based on the outcome of the intervention (no measurable residue vs residual inoperable disease), their age and/or their eligibility /suitability to receive radiotherapy.

Patients with centrally and histologically confirmed intracranial ependymoma (histology confirmed by National Reference centre for Biology and Pathology review) meeting the following criteria will be enrolled into one of interventional strata:

•Main residence in one of the participating countries,
•Age below 22 years old at the diagnosis,
•Newly diagnosed with an ependymoma WHO grade II and III, including ependymoma variants: cellular, papillary, clear-cell and tanycytic or anaplastic ependymoma.
•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 of reproductive age and childbearing potential with effective contraception (see section 4.1.2.4 Definition of highly effective methods of contraception) for the duration of their treatment and 6 months after the completion of their treatment,
•Patients and/or their parents or legal guardians willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedure

Specific inclusion criteria have been defined for each stratum of the program.

Stratum 1:
•Age > 12 months and < 22 years at time of study entry
•No residual measurable ependymoma based on the central neuroradiological review (detailed in protocol)
•Histologically confirmed WHO Grade II-III ependymoma by central pathological review
•No metastasis on spinal MRI and on CSF cytology assessments
•No previous radiotherapy
•No previous chemotherapy (except steroids)
•No co-existent unrelated disease (e.g. renal, hematological) at the time of study entry
•No medical contraindication to radiotherapy and chemotherapy,
•No signs of infection
•Adequate bone marrow function(detailed in protocol)
•Adequate liver function (detailed in protocol)
•Adequate renal function (In case of suspected compromised renal function, glomerular filtration should be measured by an isotope GFR method such as EDTA clearance or by creatinine clearance:detailed in protocol)

Stratum 2:
•Age > 1 year and <22 years at time of entry to study
•Residual non reoperable measurable ependymoma based on central neuro-radiological review (detailed in protocol)
•Histologically confirmed WHO Grade II-III ependymoma by central pathological review
•No metastasis on spinal MRI and on CS

Exclusion Criteria

All interventional stata
•Tumour entity other than primary intracranial ependymoma
•Primary diagnosis predating the opening of SIOP Ependymoma II
•Patients with WHO grade I ependymoma including ependymoma variants: myxopapillary ependymomas and subependymomas
•Patients with spinal cord location of the primary tumour
•Participation within a different trial for treatment of ependymoma
•Age = 22 years
•Contraindication to one of the IMP used in this stratum according to the SmPCs in appendix 4 of the protocol (SmPCs in appendixes are those from UK which were chosen for the assessment of the safety aspects of the study)
•Concurrent treatment with any anti-tumour agents
•Inability to tolerate chemotherapy
•Unable to tolerate intravenous hydration
•Pre-existing mucositis, peptic ulcer, inflammatory bowel disease, ascites, or pleural effusion
•Pregnancy and breast feeding

Stratum 1 and 2:
•Ineligible to receive radiotherapy
•Patient for whom imaging remains RX despite all effort to clarify the MRI conclusion
•Other severe acute or chronic medical or psychiatric condition or laboratory abnormality 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

Stratum 3:
•Pre-existing severe hepatic (liver) and/or renal (kidney) damage
Family history of severe epilepsy
•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
•Elevated Blood lactate level = 1.5 x upper limit of the normal
•Other severe acute or chronic medical or laboratory abnormality 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified