An International Clinical Program for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Ependymoma

Trial ID: NCT02265770

Interventional - Phase 2/3 - Recruiting

The overall aim of this project is to improve the outcome of patients diagnosed with ependymoma by improving and harmonising the staging and the standard of care of this patient population and to improve the investigators understanding of the underlying biology thereby informing future treatment. The program will evaluate new strategies for diagnosis (centralized reviews of pathology and imaging) and new therapeutic strategies in order to develop treatment recommendations. Patients will be stratified into different treatment subgroups according to their age, the tumour location and the outcome of the initial surgery. Each subgroup will be studied in a specific randomised study to evaluate the proposed therapeutic strategies. Stratum 1: The aim of the stratum 1 is to evaluate the clinical impact of 16-week chemotherapy regimen with VEC-CDDP following surgical resection and conformal radiotherapy in terms of progression free survival in patients who are \> 12 months and \< 22 years at diagnosis, with completely removed intra cranial Ependymoma. Stratum 2: This stratum is designed as a phase II trial for patients who are \> 12 months and \< 22 years at diagnosis, with residual disease to investigate the possible activity of HD-MTX by giving to all patients the benefit of VEC chemotherapy whilst randomising half of patients to receive additional HD-MTX. Patients will receive conformal radiotherapy (cRT). For patients who remain with a residual inoperable disease after induction chemotherapy and cRT, an 8 Gy boost of radiotherapy to the residual tumour will be delivered immediately after the end of the cRT. Stratum 3 This stratum is designed as a phase II trial to evaluate the benefit of postoperative dose intense chemotherapy administered alone or in combination with valproate in children \<12 months of age or those not eligible to receive radiotherapy .

Conditions

• Childhood Ependymoma

Interventions

• 16 weeks of VEC + CDDP
• VEC + HD-MTX
• Chemotherapy + Valproate
• Conformal radiotherapy
• VEC
• Chemotherapy
• conformal radiotherapy +/- boost

Eligibility

Inclusion criteria

• for Strata 1 and 2:
• Age \> 12 months and \< 22 years at time of study entry
• No metastasis on spinal MRI and on CSF cytology assessments
• No previous radiotherapy
• No previous chemotherapy (except steroids)
• No medical contraindication to radiotherapy and chemotherapy
• Adequate bone marrow, liver and renal functions
• Specific inclusion criteria for Stratum 1:
• No residual measurable ependymoma based on the central neuroradiological review (R0-1-2)
• Specific inclusion criteria for Stratum 2:
• Residual non reoperable measurable ependymoma based on the central neuroradiological review (R3-4)
• Inclusion criteria for Stratum 3:
• Children younger than 12 months at time of entry to study or any children ineligible to receive radiotherapy due to age at diagnosis, tumour location or clinician / parent decision and according to national criteria
• Adequate bone marrow, liver and renal functions
• No previous chemotherapy and radiotherapy
• No contraindication to chemotherapy Patients that do not fulfill the inclusion criteria of one of the interventional strata will be enrolled and followed up into an observational study and descriptive analysis will be performed.

Exclusion criteria

• for all interventional strata:
• 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
• Contraindication to one of the IMP used according to the SmPCs
• 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.
• Strata 1 and 2:
• Ineligible to receive radiotherapy
• Patient for whom imaging remains RX despite all effort to clarify the MRI conclusion
• Stratum 3:
• Pre-existing severe hepatic and/or renal damage
• Family history of severe epilepsy
• Presence of previously undiagnosed mitochondrial disorder detected by screening as part of trial
• Elevated blood ammonium and lactate level ≥ 1.5 x upper limit of the normal

Sponsor

Centre Leon Berard

Source: ClinicalTrials.gov

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