- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02265770
An International Clinical Program for the Diagnosis and Treatment of Children With Ependymoma (SIOP-EP-II)
An International Clinical Program for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Ependymoma
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 .
Study Overview
Status
Conditions
Detailed Description
The Ependymoma Program is a comprehensive program to improve the accuracy of the primary diagnosis of ependymoma and explore different therapeutic strategies in children, adolescents and young adults, accordingly. This program is opened to all patients diagnosed with ependymoma below the age of 22 years.
It will include a centralised review of pre and post-operative imaging to assess the completeness of the resection.
It will also include a central review of pathology to confirm the histological diagnosis. The biological markers 1q and 6q gain, Tenascin C status, NELL2 and LAMA2, RELA-fusion and molecular subgroup by methylation array will be prospectively assessed for prospective evaluation of disease subgroups. Further biological evaluations will be coordinated within the linked BIOMECA study.
After surgery and central review of imaging and pathology, patients will be offered the opportunity to undergo second look surgery, if possible. Patients will be enrolled in one of 3 different strata according to the outcome of the initial surgical resection (residual disease vs no residual disease), their age or eligibility / suitability to receive radiotherapy. These 3 different strata correspond to 3 therapeutic strategies according to the patient status.
- Stratum 1 is designed as a randomised phase III study for patients who have had a complete resection, with no measurable residual disease (as confirmed by centrally reviewed MRI) and are > 12 months and < 22 years at diagnosis. Those patients will be randomised to receive conformal radiotherapy followed by either 16 weeks of chemotherapy with VEC-CDDP, or observation.
- Stratum 2 is designed as a randomised phase II study for patients who have inoperable measurable residual disease and who are > 12 months and < 22 years at diagnosis. Those patients will be randomised to two different treatment schedules of chemotherapy either with VEC or VEC+ high dose methotrexate (VEC +HD-MTX). After completion of the frontline chemotherapy, patients will be assessed for response (MRI) and will receive second look surgery when feasible. For those patients who remain unresectable with residual disease despite frontline chemotherapy and for whom second line surgery is not feasible, there will be a study of the safety of a radiotherapy boost of 8 Gy that will be administered to the residual tumour immediately after the completion of the conformal radiotherapy. Patients without evidence of residual disease after the chemotherapy and/or a second look surgery are not eligible for radiotherapy boost. All patients who have not shown progression under chemotherapy will receive, as maintenance therapy, a 16 week course of VEC -CDDP following completion of radiotherapy.
- Stratum 3 is designed as a randomised phase II chemotherapy study in children <12 months of age or those not eligible to receive radiotherapy. These patients will be randomised to receive a dose dense chemotherapy alternating myelosuppressive and relatively non-myelosuppressive drugs at 2 weekly intervals, with or without, the addition of the histone deacetylase inhibitor, valproate.
Registry: Patients that do not fulfil the inclusion criteria of one of the interventional strata will be enrolled and followed up via an observational study which will be analysed descriptively.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Pierre LEBLOND, MD
- Phone Number: +33 4 69 16 66 14
- Email: pierre.leblond@lyon.unicancer.fr
Study Locations
-
-
-
Graz, Austria, 8036
- Recruiting
- Medical University of Graz-Department of Pediatrics and Adolescent Medicine
-
Principal Investigator:
- Martin Benesch, MD
-
Contact:
- Martin Benesch, MD
- Phone Number: +43 (0) 316/385-80427
- Email: martin.benesch@klinikum-graz.at
-
-
-
-
-
Liege, Belgium, 4000
- Recruiting
- CHR de la Citadelle
-
Contact:
- Caroline Piette
- Phone Number: +32 4 225 60 97
- Email: caroline.piette@chrcitadelle.be
-
Principal Investigator:
- Caroline Piette, MD
-
-
-
-
-
Brno, Czechia, 61300
- Recruiting
- University Hospital Brno
-
Principal Investigator:
- Jaroslav Sterba, MD
-
Contact:
- Jaroslav Sterba, MD
- Phone Number: +420 532 234 600/755
- Email: jsterb@fnbrno.cz
-
-
-
-
-
Aarhus, Denmark, 8200
- Recruiting
- Aarhus University Hospital
-
Contact:
- Pernille Wendtland Edslev
- Phone Number: +45 78451701
- Email: pernedsl@rm.dk
-
Principal Investigator:
- Pernille Wendtland Edslev, MD
-
-
-
-
-
Limoges, France
- Recruiting
- CHU Limoges
-
Contact:
- Christophe Piguet, MD
- Phone Number: +33 5 55 05 68 01
- Email: christophe.piguet@chu-limoges.fr
-
Principal Investigator:
- Christophe PIGUET, MD
-
Nice, France, 06202
- Recruiting
- CHU Nice - Hôpital de l'Archet 2
-
Contact:
- Christine SOLER, MD
- Phone Number: +33492039268
- Email: soler.c@chu-nice.fr
-
Saint-Denis, France, 97400
- Recruiting
- CHU La Réunion
-
Principal Investigator:
- Yves REGUERRE, MD
-
Contact:
- Yves REGUERRE, MD
- Email: Yves.reguerre@chu-reunion.fr
-
-
Bas-Rhin
-
Strasbourg, Bas-Rhin, France, 67098
- Recruiting
- CHRU Strasbourg - Hôpital de Hautepierre
-
Contact:
- Natacha Entz-Werle, MD
- Phone Number: +33 3 88 12 83 96
- Email: natacha.entz-werle@chru-strasbourg.fr
-
Principal Investigator:
- Natacha ENTZ-WERLE, MD
-
-
Bouches-du-Rhône
-
Marseille, Bouches-du-Rhône, France, 13385
- Recruiting
- AP-HM - Hôpital d'Enfants de La Timone
-
Contact:
- Jean-Claude Gentet, MD
- Phone Number: +33 4 91 38 68 21
- Email: jean-claude.gentet@ap-hm.fr
-
Principal Investigator:
- Jean-Claude Gentet, MD
-
-
Côte d'Or
-
Dijon, Côte d'Or, France, 21079
- Recruiting
- CHU Dijon - Hôpital des Enfants
-
Principal Investigator:
- Claire BRIANDET, MD
-
Contact:
- Claire Briandet, MD
- Phone Number: +33 03 80 29 34 14
- Email: claire.briandet@chu-dijon.fr
-
-
Doubs
-
Besançon, Doubs, France, 25030
- Recruiting
- CHRU Besancon - Hopital Jean Minjoz
-
Contact:
- Véronique Laithier, MD
- Phone Number: +33 3 81 66 81 66
- Email: vlaithier@chu-besançon.fr
-
Principal Investigator:
- Véronique LAITHIER, MD
-
-
Finistère
-
Brest, Finistère, France, 29609
- Recruiting
- CHRU Brest - Hopital Morvan
-
Contact:
- Liana-Stefania Carausu, MD
- Phone Number: +33 2 98 22 33 81
- Email: liana.carausu@chu-brest.fr
-
Sub-Investigator:
- Philippe Le Moine, MD
-
Principal Investigator:
- Liana-Stefania Carausu
-
-
Gironde
-
Bordeaux, Gironde, France, 33000
- Recruiting
- CHU de Bordeaux-Hôpital des enfants Pellegrin
-
Contact:
- Céline Icher, MD
- Phone Number: +33 5 57 82 04 34
- Email: celine.icher@chu-bordeaux.fr
-
Principal Investigator:
- Céline ICHER, MD
-
-
Haute-Garonne
-
Toulouse, Haute-Garonne, France, 31059
- Recruiting
- CHU de Toulouse - Hôpital des Enfants
-
Principal Investigator:
- Anne-Isabelle BERTOZZI-SALAMON, MD
-
Contact:
- Anne-Isabelle Bertozzi-Salamon, MD
- Phone Number: +33 5 34 55 86 13
- Email: bertozzi.ai@chu-toulouse.fr
-
-
Herault
-
Montpellier, Herault, France, 34295
- Recruiting
- CHRU MONTPELLIER - Hôpital Arnaud de Villeneuve
-
Principal Investigator:
- Gilles PALENZUELA, MD
-
Contact:
- Nicolas Sirvent, MD
- Phone Number: +33 4 67 33 65 19
- Email: n-sirvent@chu-montpellier.fr
-
Sub-Investigator:
- Nicolas Sirvent, MD
-
-
Ile-De-France
-
Paris, Ile-De-France, France, 75005
- Recruiting
- Fondation Institut Curie
-
Contact:
- François Doz, MD
- Phone Number: +33 1 44 32 46 01
- Email: francois.doz@curie.fr
-
Principal Investigator:
- François Doz, MD
-
-
Ile-de-France
-
Villejuif, Ile-de-France, France, 94805
- Recruiting
- Institut Gustave Roussy
-
Contact:
- Léa Guérrini-Rousseau, MD
- Phone Number: +33 1 42 11 42 11
- Email: lea.guerrini-rousseau@gustaveroussy.fr
-
Principal Investigator:
- Léa Guérrini-Rousseau, MD
-
-
Ille-et-Vilaine
-
Rennes, Ille-et-Vilaine, France, 35203
- Recruiting
- CHU de Rennes - Hôpital Sud
-
Contact:
- Charline Normand, MD
- Phone Number: +33 2 99 26 58 35
- Email: charline.normand@chu-rennes.fr
-
Principal Investigator:
- Céline Chappe, MD
-
-
Indre-et-Loire
-
Tours, Indre-et-Loire, France, 37044
- Recruiting
- CHRU Tours - Hôpital Clocheville
-
Principal Investigator:
- Pascale BLOUIN, MD
-
Contact:
- Pascale Blouin, MD
- Phone Number: +33 02 47 47 49 72
- Email: p.blouin@chu-tours.fr
-
-
Isère
-
La Tronche, Isère, France, 38700
- Recruiting
- CHU GRENOBLE - Hôpital Couple-Enfant
-
Contact:
- Anne Pagnier, MD
- Phone Number: +33 4 76 76 54 69
- Email: apagnier@chu-grenoble.fr
-
Principal Investigator:
- Anne PAGNIER, MD
-
-
Loire
-
Saint-Etienne, Loire, France, 42055
- Recruiting
- CHRU Saint-Etienne
-
Contact:
- Sandrine Thouvenin, MD
- Phone Number: +33 04 77 82 88 08
- Email: sandrine.thouvenin@chu-st-etienne.fr
-
Principal Investigator:
- Sandrine Thouvenin, MD
-
-
Maine-et-Loire
-
Angers, Maine-et-Loire, France, 49100
- Recruiting
- CHU Angers
-
Contact:
- Emilie De Carli, MD
- Phone Number: +33 2 41 35 38 63
- Email: EmDecarli@chu-angers.fr
-
Principal Investigator:
- Emilie DE CARLI, MD
-
-
Marne
-
Reims, Marne, France, 51092
- Recruiting
- CHU REIMS - American Memorial Hospital
-
Contact:
- Claire Pluchart, MD
- Email: cpluchart@chu-reims.fr
-
Principal Investigator:
- Claire PLUCHART, MD
-
-
Meurthe-et-Moselle
-
Vandoeuvre-les-Nancy, Meurthe-et-Moselle, France, 54511
- Recruiting
- CHU NANCY - Brabois Hôpital d'Enfants
-
Contact:
- Pascal Chastagner, MD
- Phone Number: +33 3 83 15 46 37
- Email: p.chastagner@chu-nancy.fr
-
Sub-Investigator:
- Ludovic MANSUY, MD
-
Principal Investigator:
- Pascal CHASTAGNER, MD
-
-
Nord
-
Lille, Nord, France, 59000
- Recruiting
- Centre Oscar Lambret
-
Contact:
- Hélène SUDOUR, MD
- Phone Number: +33 3 20 29 59 56
- Email: h-sudour@o-lambret.fr
-
Principal Investigator:
- Hélène SUDOUR, MD
-
-
Puy-de-Dôme
-
Clermont-Ferrand, Puy-de-Dôme, France, 63003
- Recruiting
- CHU Clermont- Ferrand - Hôpital Estaing
-
Principal Investigator:
- Justyna KANOLD, MD
-
Contact:
- Catherine Paillard, MD
- Phone Number: +33 4 73 75 00 09
- Email: cpaillard@chu-clermontferrand.fr
-
-
Rhône
-
Lyon, Rhône, France, 69473
- Recruiting
- Centre Leon Berard
-
Principal Investigator:
- Pierre LEBLOND, MD
-
Contact:
- Pierre LEBLOND, MD
- Phone Number: +33 4 69 16 66 14
- Email: pierre.leblond@lyon.unicancer.fr
-
-
Seine Maritime
-
Rouen, Seine Maritime, France, 76031
- Recruiting
- CHU Rouen - Hôpital Charles Nicolle
-
Contact:
- Pascale Schneider, MD
- Phone Number: +33 02 32 88 81 91
- Email: pascale.schneider@chu-rouen.fr
-
Principal Investigator:
- Pascale SCHNEIDER, MD
-
-
Somme
-
Amiens, Somme, France, 80054
- Recruiting
- CHU AMIENS-PICARDIE - Hôpital Nord
-
Contact:
- Catherine Devoldere, MD
- Phone Number: +33 3 22 66 89 50
- Email: devoldere.catherine@chu-amiens.fr
-
Principal Investigator:
- Catherine Devoldere, MD
-
-
Vienne
-
Poitiers, Vienne, France, 86021
- Recruiting
- CHU POITIERS - Hôpital de la Milétrie
-
Contact:
- Frédéric Millot, MD
- Phone Number: +33 5 49 44 30 78
- Email: f.millot@chu-poitiers.fr
-
Principal Investigator:
- Frédéric MILLOT, MD
-
-
-
-
-
Hamburg, Germany, 20246
- Recruiting
- University Medical Center Hamburg-Eppendorf
-
Contact:
- Stefan Rutkowski, MD
- Email: s.rutkowski@uke.de
-
Principal Investigator:
- Stefan Rutkowski, MD
-
-
-
-
-
Dublin, Ireland
- Recruiting
- Our Lady's Children's Hospital
-
Contact:
- Michael Capra, MD
- Phone Number: +353 1 409 6659
- Email: Michael.capra@olhsc.ie
-
Principal Investigator:
- Michael Capra, MD
-
-
-
-
-
Milan, Italy, 20133
- Recruiting
- Fondazione IRCCS Istituto Nazionale dei Tumori
-
Contact:
- Maura Massimino, MD
- Phone Number: +39 0223902593
- Email: Maura.Massimino@istitutotumori.mi.it
-
Principal Investigator:
- Maura Massimino, MD
-
-
-
-
-
Utrecht, Netherlands
- Recruiting
- Princess Máxima Center for Pediatric Oncology
-
Contact:
- Jasper van der Lugt, MD
- Phone Number: +31 6 1855 96 94
- Email: J.vanderLugt@prinsesmaximacentrum.nl
-
Principal Investigator:
- Jasper van der Lugt, MD
-
-
-
-
-
Bergen, Norway, 5021
- Recruiting
- Department of Paediatric, Haukeland University Hospital
-
Contact:
- Ingrid Kristin Torsvik, MD, PhD
- Phone Number: +47 5597 5199
- Email: Ingrid.kristin.torsvik@helse-bergen.no
-
Principal Investigator:
- Ingrid Kristin Torsvik, MD, PhD
-
-
-
-
-
Ljubljana, Slovenia, 1000
- Not yet recruiting
- University Medical Center Ljubljana
-
Contact:
- Lidija Kitanovski, MD
- Phone Number: + 386 1 522 9215 / 522 9256
- Email: lidija.kitanovski@kclj.si
-
Principal Investigator:
- Lidija Kitanovski, MD
-
-
-
-
-
Sevilla, Spain, 41071
- Recruiting
- Hospitales Universitarios Virgen Macarena y Virgen del Rocío Avda
-
Contact:
- Ana Fernández-Teijeiro, MD
- Phone Number: +34677903132
- Email: anateijeiro@hotmail.com
-
Principal Investigator:
- Ana Fernández-Teijeiro, MD
-
-
-
-
-
Lund, Sweden, 22185
- Not yet recruiting
- Skane University Hospital
-
Principal Investigator:
- Helena Mörse, MD
-
Contact:
- Helena Mörse, MD
- Phone Number: +46 46 178281
- Email: Helena.Morse@skane.se
-
-
-
-
-
Zurich, Switzerland, 8032
- Recruiting
- University Children's Hospital
-
Contact:
- Nicolas Gerber, MD
- Phone Number: +41 44 266 31 17
- Email: nicolas.gerber@kispi.uzh.ch
-
Principal Investigator:
- Nicolas Gerber, MD
-
-
-
-
-
Nottingham, United Kingdom
- Recruiting
- Queen's Medical Centre
-
Contact:
- Richard Grundy, MD
- Phone Number: +44 115 8230620
- Email: richard.grundy@nottingham.ac.uk
-
Principal Investigator:
- Richard Grundy, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
After Initial surgery, 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 meeting the following criteria will be enrolled into one of interventional stratum:
- Age < 22 years old at diagnosis
- Newly diagnosed intracranial ependymoma of WHO grade II-III confirmed by central pathological review
- 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 for the duration of their treatment and 6 months after the completion of their treatment
- No contraindication to the use if one of the study drugs proposed by the protocol
- Patients and/or their parents or legal guardians willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedure
- No co-existent unrelated disease at the time of study entry that would render the patient unable to receive chemotherapy
- No signs of infection.
Common 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Stratum 1 arm A
Conformal radiotherapy followed by 16 weeks of VEC + CDDP.
|
Days 1-36-71-106: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; Days 1-3-36-38-71-73-106-108: Etoposide: 100 mg/m² infused over 60 minutes; Days 1-36-71-106: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; Days 22-57-92: Cisplatin: 80 mg/m² over 4 hours + Vincristine:1.5 mg/m² (maximal dose 2 mg) i.v.
Other Names:
Conformal radiotherapy: 59.4Gy (children <18 months or with risk factors: 54Gy).
Daily fraction 1.8 Gy, 5 fractions / week.
|
Active Comparator: Stratum 1 arm B
Conformal radiotherapy.
|
Conformal radiotherapy: 59.4Gy (children <18 months or with risk factors: 54Gy).
Daily fraction 1.8 Gy, 5 fractions / week.
|
Experimental: Stratum 2 arm A
VEC + HD-MTX followed by conformal radiotherapy +/- boost
|
Days 1-22-43: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; Days 1-3-22-24-43-45: Etoposide: 100 mg/m² infused over 60 minutes; Days 1-22-43: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; Days 15-36-57: Administer methotrexate at 8000 mg/m² as a 24 hour IV infusion on days 15-36-57.
10% of the dose should be given over the first hour and 90% over the remaining 23 hours.
The infusion must finish at 24 hours even if it has not been completed.
Other Names:
Conformal radiotherapy: 59.4Gy (children <18 months or with risk factors: 54Gy). Daily fraction 1.8 Gy, 5 fractions / week. In case of persistent residue : Boost of radiation 8 Gy in 2 equivalent fractions |
Active Comparator: Stratum 2 arm B
VEC followed by conformal radiotherapy +/- boost
|
Conformal radiotherapy: 59.4Gy (children <18 months or with risk factors: 54Gy). Daily fraction 1.8 Gy, 5 fractions / week. In case of persistent residue : Boost of radiation 8 Gy in 2 equivalent fractions
D1: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; D1-D3: Etoposide: 100 mg/m² infused over 60 minutes; D1: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; D22: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; D22-D24: Etoposide: 100 mg/m² infused over 60 minutes; D22: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes; D43: Vincristine: 1.5 mg/m² (maximal dose 2 mg) i.v.; D43-D45: Etoposide: 100 mg/m² infused over 60 minutes; D43: Cyclophosphamide: 3000 mg/m² in 3 divided infusions (1000 mg/m²/infusion) infused over 60 minutes
Other Names:
|
Experimental: Stratum 3 arm A
Chemotherapy + Valproate.
|
Days 1-57-113-169-225-281-337: Vincristine and Carboplatin; Days 15-71-127-183-239-295-351: Vincristine and Methotrexate; Days 29-85-141-197-253-309-365: Vincristine and Cyclophosphamide; Days 43-44-99-100-154-155-211-212-267-268-323-324-379-380: Cisplatin 2-day continuous infusion. Valproate: initial dose 30 mg/kg/day for two weeks in 2 divided doses (BID 15 mg/kg). Increasing weekly up to 40 - 50 - 60 mg/kg/day in 2 divided doses.
Other Names:
|
Active Comparator: Stratum 3 arm B
Chemotherapy
|
Days 1-57-113-169-225-281-337: Vincristine and Carboplatin; Days 15-71-127-183-239-295-351: Vincristine and Methotrexate; Days 29-85-141-197-253-309-365: Vincristine and Cyclophosphamide; Days 43-44-99-100-154-155-211-212-267-268-323-324-379-380: Cisplatin 2-day continuous infusion.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gross Total Resection rate
Time Frame: 3 years
|
Overall program, depends on the stratum (from 0.5 years to 3 years)
|
3 years
|
Progression-Free Survival
Time Frame: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 4.5 years
|
from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 4.5 years
|
|
Number of treatment responders
Time Frame: 15 months after final patient inclusion
|
Objective response to chemotherapy is measured based on SIOP-E Neuro Imaging guidelines.
|
15 months after final patient inclusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants undergoing a second-look surgery
Time Frame: 9 months
|
9 months
|
|
Overall Survival
Time Frame: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3 years after the final patient inclusion
|
from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3 years after the final patient inclusion
|
|
Quality of Survival
Time Frame: from date of randomization up to 5 years after the end of treatment
|
Questionnaire
|
from date of randomization up to 5 years after the end of treatment
|
Evaluation of neuropsychological morbidity
Time Frame: from date of randomization up to 5 years after the end of treatment
|
Scores: evaluation of processing speed (WPPSI-III, WISC-IV, WAIS-IV), verbal skills (WPPSI-III, WISC-IV, WAIS-IV), fluid intelligence (WPPSI-III / Ravens, WISC-IV / Ravens, WAIS-IV / Ravens), working memory (K-ABC / Children's Memory Scale, WISC-IV, WAIS-IV), visuo-spatial abilities (Beery-Buktenica Developmental Test of Visual-Motor Integration/Wide Range Assessment of Visual Motor Abilities - WRAVMA), regarding ability (as to national policy/WIAT-II) and motoric speed (Perdue Pegboard)
|
from date of randomization up to 5 years after the end of treatment
|
Comparison of neuroendocrine morbidity
Time Frame: from date of randomization up to 5 years after the end of treatment
|
Weight, height and head circumference, Tanner age, early and delayed pubertal onset, blood sample analysis (evaluation of TSH, fT4, LH and FSH, oestradiol, testosterone, insulin-like growth factor 1)
|
from date of randomization up to 5 years after the end of treatment
|
Number of participants with adverse events as a measure of safety and tolerability
Time Frame: from date of randomization up to 5 years after the end of treatment
|
Determination of short and long term safety and toxicity of frontline chemotherapy based on proportion of patients experiencing toxicity grade 3 to 4 (adverse events)
|
from date of randomization up to 5 years after the end of treatment
|
Radiotherapy-free survival rate
Time Frame: from date of randomization until the date of first documented progression or date of death from any cause, or radiotherapy intervention, whichever came first, up to 2.5 years after the final patient inclusion
|
from date of randomization until the date of first documented progression or date of death from any cause, or radiotherapy intervention, whichever came first, up to 2.5 years after the final patient inclusion
|
|
Efficacy in each molecular sub-group
Time Frame: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3 years after the final patient inclusion
|
Efficacy in each molecular subtype described in terms of Progression-Free survival and Overall Survival
|
from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3 years after the final patient inclusion
|
Concordance between central and local radiological assessment of the efficacy of post-operative chemotherapy
Time Frame: 15 months after final patient inclusion
|
Proportion of patients in whom the result of the central radiological review confirms the local review
|
15 months after final patient inclusion
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Pierre LEBLOND, MD, IHOP
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Ependymoma
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- GABA Agents
- Anticonvulsants
- Antimanic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Cyclophosphamide
- Carboplatin
- Etoposide
- Etoposide phosphate
- Cisplatin
- Valproic Acid
- Methotrexate
- Vincristine
Other Study ID Numbers
- SIOP Ependymoma II (ET-13-002)
- 2013-002766-39 (EudraCT Number)
- VHP358 (Other Identifier: CTFG (HMA))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Childhood Ependymoma
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Infratentorial Ependymoma | Childhood Supratentorial Ependymoma | Newly Diagnosed Childhood EpendymomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Childhood Ependymoma | Childhood Infratentorial Ependymoma | Childhood Supratentorial Ependymoma | Recurrent Childhood Cerebellar Astrocytoma | Recurrent Childhood Cerebral Astrocytoma | Recurrent Childhood Subependymal Giant Cell Astrocytoma | Childhood Mixed Glioma | Childhood Oligodendroglioma and other conditionsUnited States, Canada, Australia
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Childhood Medulloblastoma | Recurrent Childhood Ependymoma | Childhood Atypical Teratoid/Rhabdoid Tumor | Ependymoma | Childhood Craniopharyngioma | Childhood Grade I Meningioma | Childhood Grade II Meningioma | Childhood Grade III Meningioma | Childhood Infratentorial Ependymoma | Childhood... and other conditionsUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
National Cancer Institute (NCI)CompletedRecurrent Childhood Medulloblastoma | Recurrent Childhood Ependymoma | Recurrent Childhood Anaplastic Astrocytoma | Recurrent Childhood Brain Stem Glioma | Recurrent Childhood Giant Cell Glioblastoma | Recurrent Childhood Glioblastoma | Recurrent Childhood Gliosarcoma | Recurrent Childhood OligodendrogliomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Childhood Medulloblastoma | Recurrent Childhood Ependymoma | Childhood Atypical Teratoid/Rhabdoid Tumor | Childhood Grade I Meningioma | Childhood Grade II Meningioma | Childhood Grade III Meningioma | Childhood Infratentorial Ependymoma | Childhood Supratentorial Ependymoma | Recurrent Childhood... and other conditionsUnited States
-
Sue O'DorisioNational Cancer Institute (NCI); Ride for KidsWithdrawnRecurrent Childhood Medulloblastoma | Recurrent Childhood Ependymoma | Untreated Childhood Brain Stem Glioma | Untreated Childhood Medulloblastoma | Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor | Adult Anaplastic Astrocytoma | Adult Anaplastic Ependymoma | Adult Anaplastic Oligodendroglioma and other conditionsUnited States
-
The Hospital for Sick ChildrenActive, not recruitingChildhood Solid Tumor | Recurrent Childhood CNS Tumor | Ependymoma, Recurrent ChildhoodUnited States, Canada, Australia
-
National Cancer Institute (NCI)CompletedRecurrent Childhood Medulloblastoma | Recurrent Childhood Ependymoma | Childhood Choroid Plexus Tumor | Childhood Craniopharyngioma | Childhood Ependymoblastoma | Childhood Grade I Meningioma | Childhood Grade II Meningioma | Childhood Grade III Meningioma | Childhood High-grade Cerebellar Astrocytoma | Childhood High-grade Cerebral Astrocytoma and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Childhood Medulloblastoma | Recurrent Childhood Ependymoma | Childhood Atypical Teratoid/Rhabdoid Tumor | Childhood Choroid Plexus Tumor | Childhood Craniopharyngioma | Childhood Ependymoblastoma | Childhood Grade I Meningioma | Childhood Grade II Meningioma | Childhood Grade III Meningioma | Childhood High-grade Cerebellar Astrocytoma and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Childhood Medulloblastoma | Recurrent Childhood Ependymoma | Childhood Choroid Plexus Tumor | Childhood Craniopharyngioma | Childhood Ependymoblastoma | Childhood Grade I Meningioma | Childhood Grade II Meningioma | Childhood Grade III Meningioma | Childhood High-grade Cerebellar Astrocytoma | Childhood High-grade Cerebral Astrocytoma and other conditionsUnited States
Clinical Trials on 16 weeks of VEC + CDDP
-
Universidade Federal do Rio de JaneiroRecruiting
-
EVYD TechnologyRaja Isteri Pengiran Anak Saleha HospitalCompletedDiabetes Mellitus, Type IISingapore
-
Stanford UniversityNational Institute on Aging (NIA)Active, not recruitingHoarding Disorder | Hoarding | ClutterUnited States
-
Korea Otsuka Pharmaceutical Co., Ltd.CompletedDiabetic NephropathyKorea, Republic of
-
University Health Network, TorontoActive, not recruitingAxial SpondyloarthritisCanada
-
University of California, DavisNational Mango BoardCompletedWrinkle | Skin RedUnited States
-
National Taiwan University HospitalNational Science Council, Taiwan; Department of Health, Executive Yuan, R.O...Completed
-
Vecmedical Spain, S.L.RecruitingRectal Polyp | Rectal Lesion | Sessile Colonic Polyp | Rectal Polyps | Pedunculated Colorectal PolypsSpain