Clinical trial • Phase III • Oncology

VINORELBINE for Ewing sarcoma

Phase III trial of VINORELBINE for Ewing sarcoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Ewing sarcoma
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
20-03-2025
First CTIS Authorization Date
14-07-2025

Trial design

Randomised, vdc/ie backbone chemotherapy versus vdc/ie plus regorafenib (randomisation a); radiotherapy dose escalation/comparisons for definitive and post-operative settings (randomisations b1 and b2); maintenance vinorelbine plus cyclophosphamide versus no maintenance (randomisation c). doses and schedules are not specified in the ctis summary.-controlled Phase III trial in Denmark, Spain, Netherlands and others.

Randomised
Yes
Comparator
VDC/IE backbone chemotherapy versus VDC/IE plus regorafenib (Randomisation A); radiotherapy dose escalation/comparisons for definitive and post-operative settings (Randomisations B1 and B2); maintenance vinorelbine plus cyclophosphamide versus no maintenance (Randomisation C). Doses and schedules are not specified in the CTIS summary.
Target Sample Size
402

Eligibility

Recruits 402 paediatric patients.

Pregnancy Exclusion
Pregnant or breastfeeding women
Vulnerable Population
Vulnerable populations included: paediatric patients (minimum age ≥2 years). The protocol selects vulnerable subjects (isVulnerablePopulationSelected = true). Written informed consent must be obtained from the patient and/or the parent/legal guardian. Age-appropriate information sheets, assent forms and consent forms are provided for multiple age groups (examples in documents: under 12; 5-9 yr; 10-14 yr; 12-15 yr; 13-17 yr; 15-17 yr; adult/over 16) and parent/guardian versions. Country-specific ICF/SIS documents are provided (documents available for Denmark, Spain, The Netherlands, France, Norway and English-language materials are present), indicating local-language and age-stratified consent/assent handling and parent/legal guardian consenting where applicable.

Inclusion criteria

  • {"criterion_text":"-Study Entry: 1. Any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or round cell sarcomas which are ‘Ewing’s-like’ but negative for EWSR1-Fli gene rearrangement"}
  • {"criterion_text":"-Randomisation B1 & B2: 5. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active"}
  • {"criterion_text":"-Randomisation B1 & B2: 6. Written informed consent from the patient and/or the parent/legal guardian"}
  • {"criterion_text":"-Randomisation A: To be further defined on completion of the externally sponsored phase 1b study. substantial modification will be submitted to the relevant competent authority and ethics committee(s) to include these details prior to the opening of Randomisation A."}
  • {"criterion_text":"-Randomisation C: 1. Entered into the INTER-EWING-1 study"}
  • {"criterion_text":"-Randomisation C: 2. Received induction/ consolidation chemotherapy with a VDC/IE/VC/VAI/BuMel based regimen"}
  • {"criterion_text":"-Randomisation C: 3. Have responded to induction treatment and not progressed"}
  • {"criterion_text":"-Randomisation C: 4. Medically fit to receive treatment"}
  • {"criterion_text":"-Randomisation C: 5. Absence of severe vincristine neuropathy – i.e. requiring discontinuation of vincristine treatment"}
  • {"criterion_text":"-Randomisation C: 6. Adequate liver function: bilirubin <3 x ULN and ALT or AST < 5 x ULN"}
  • {"criterion_text":"-Randomisation C: 7. Documented negative pregnancy test for female patients of childbearing potential"}
  • {"criterion_text":"-Randomisation B1: 1. Patients requiring definitive radical radiotherapy to primary tumour site as sole local therapy following discussion by local multidisciplinary team (see INTER-EWING-1 QUARTET RTQA guidelines on factors to be considered for definitive radiotherapy). This includes patients who have undergone an R2 resection of the primary tumour (macroscopic residual tumour), requiring definitive radical radiotherapy"}
  • {"criterion_text":"-Randomisation C: 8. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active (see section 5)"}
  • {"criterion_text":"-Randomisation C: 9. Written informed consent from the patient and/or the parent/legal guardian"}
  • {"criterion_text":"-Randomisation B2: 1. Patients requiring post-operative radiotherapy following discussion by local multidisciplinary team at the multidisciplinary team meeting"}
  • {"criterion_text":"-Study Entry: 2. Age ≥ 2 years"}
  • {"criterion_text":"-Study entry: 3. Written informed consent from the patient and/or the parent/legal guardian"}
  • {"criterion_text":"-Randomisation B1 & B2: 1. Entered into the INTER-EWING-1 study"}
  • {"criterion_text":"-Randomisation B1 & B2: 2. Received induction/consolidation chemotherapy with a VDC/IE/VC/VAI/BuMel based regimen"}
  • {"criterion_text":"-Randomisation B1 & B2: 3. Patient assessed as medically fit to receive the radiotherapy"}
  • {"criterion_text":"-Randomisation B1 & B2: 4. Documented negative pregnancy test for female patients of childbearing potential"}

Exclusion criteria

  • {"criterion_text":"-Study entry: 1. Previous malignancy"}
  • {"criterion_text":"-Randomisation C: 1. Urinary outflow obstruction that cannot be relieved prior to starting treatment"}
  • {"criterion_text":"-Randomisation C: 2. Uncontrolled significant inter-current illness or active infection"}
  • {"criterion_text":"-Randomisation C: 3. Active inflammation of the urinary bladder (cystitis)"}
  • {"criterion_text":"-Randomisation C: 4. Known contraindication or hypersensitivity to any of the treatments or excipients"}
  • {"criterion_text":"-Randomisation C: 5. Pregnant or breastfeeding women"}
  • {"criterion_text":"-Randomisation B1 & B2: 1. Previous radiotherapy to the same site"}
  • {"criterion_text":"-Randomisation B1 & B2: 2. Pregnant or breastfeeding women"}
  • {"criterion_text":"-Randomisation B1 & B2: 3. BuMel high dose chemotherapy within previous 10 weeks"}
  • {"criterion_text":"-Randomisation B1: 1. Patients who have had a R1 or R0 surgical resection of their tumour"}
  • {"criterion_text":"-Randomisation B1: 2. Previous high dose chemotherapy including busulfan when specified dose constraints to critical organs cannot be met"}
  • {"criterion_text":"-Randomisation B2: 1. R2 resection (macroscopic residual tumour)"}
  • {"criterion_text":"-Randomisation B2: 2. Patients treated by surgery with wide resection (R0 and all tissues involved by the prechemotherapy tumour volume have been completely resected) and have good histological response (< 10% viable cells), small tumour volume (< 200 mls at diagnosis), of the limb."}
  • {"criterion_text":"-Randomisation A: To be further defined on completion of the externally sponsored phase 1b study. substantial modification will be submitted to the relevant competent authority and ethics committee(s) to include these details prior to the opening of Randomisation A."}

Endpoints

Primary endpoints

  • {"endpoint_text":"-The primary end point for all randomisations is Event-free survival, defined as the time from randomisation until first failure event","definition_or_measurement_approach":"Event-free survival defined as the time from randomisation until first failure event"}

Secondary endpoints

  • {"endpoint_text":"-Randomisation A: Induction chemotherapy Overall Survival, Toxicity, Cancer Quality of Life Measures, Histological response (if surgery is performed)","definition_or_measurement_approach":"Overall Survival, Toxicity, Cancer Quality of Life Measures, and histological response if surgery performed (as listed for Randomisation A)"}
  • {"endpoint_text":"-Randomisations B1 & B2: Radiotherapy Local Failure-Free Survival Time, Overall Survival, Toxicity, Achievement of local control, Acute post-radiotherapy toxicity, Late toxicity, Cancer Quality of Life Measures","definition_or_measurement_approach":"Local Failure-Free Survival Time, Overall Survival, toxicity measures, measures of local control, acute and late radiotherapy toxicity, and cancer QoL (as listed for Randomisations B1 & B2)"}
  • {"endpoint_text":"-Randomisation C: Maintenance therapy Overall Survival, Toxicity, Cancer Quality of Life Measures","definition_or_measurement_approach":"Overall Survival, Toxicity, Cancer Quality of Life Measures for maintenance therapy (Randomisation C)"}

Recruitment

Planned Sample Size
402
Recruitment Window Months
90
Consent Approach
Written informed consent required from the patient and/or parent/legal guardian. Age-specific participant information sheets and consent/assent forms are provided for multiple child and adolescent age bands (examples: under 12, 5-9 yr, 10-14 yr, 12-15 yr, 13-17 yr, 15-17 yr, adult/over 16) and separate parent/guardian forms. Country-specific ICF and SIS documents exist for Denmark, Spain, The Netherlands, France and Norway (and English-language versions), indicating local-language materials and parent/legal guardian consent where applicable.

Geography

Total Number Of Sites
63
Total Number Of Participants
498

Denmark

Earliest CTIS Part Ii Submission Date
15-06-2025
Latest Decision Or Authorization Date
14-07-2025
Processing Time Days
29
Number Of Sites
3
Number Of Participants
40

Sites

Site Name
Rigshospitalet
Department Name
Department of Paediatric and Adolescent Medicine
Contact Person Name
Lisa Hjalgrim
Contact Person Email
Lisa.hjalgrim@regionh.dk
Site Name
Region Midtjylland
Department Name
Department of Oncology
Contact Person Name
Ninna Aggerholm Pedersen
Contact Person Email
ninnpede@rm.dk
Site Name
Region Midtjylland
Department Name
Department of Paediatric and Adolescent Medicine
Contact Person Name
Louise Lindholdt Hansen
Contact Person Email
loliha@rm.dk

Spain

Earliest CTIS Part Ii Submission Date
09-05-2025
Latest Decision Or Authorization Date
17-07-2025
Processing Time Days
69
Number Of Sites
17
Number Of Participants
188

Sites

Site Name
Hospital Universitario La Paz
Department Name
Paediatric Haemato-Oncology
Contact Person Name
Pedro Rubio Aparicio
Contact Person Email
pedro.rubio@salud.madrid.org
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Oncology Department
Contact Person Name
Raúl Terés Lleida
Contact Person Email
RTeres@santpau.cat
Site Name
Hospital Universitario Central De Asturias
Department Name
Oncology Department
Contact Person Name
Maria del Pilar Solis Hernandez
Site Name
Hospital Universitario De Canarias
Department Name
Oncology Department
Contact Person Name
Josefina Cruz Jurado
Contact Person Email
jcruzjurado@gmail.com
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
Paediatric Oncology Department
Contact Person Name
Alicia Castañeda Heredia
Contact Person Email
alicia.castanedah@sjd.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Paediatric Oncology Department
Contact Person Name
Catilina Márquez Vega
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Paediatric Oncology Department
Contact Person Name
Antonio Juan Ribelles
Contact Person Email
juan_antrib@gva.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology Department
Contact Person Name
Claudia Valverde Morales
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Oncology Department
Contact Person Name
Rosa Álvarez Álvarez
Contact Person Email
ralvareza@salud.madrid.org
Site Name
Hospital Universitario Miguel Servet
Department Name
Paediatric Oncology Department
Contact Person Name
Carmen Rodríguez -Vigil Iturrate
Site Name
Hospital Infantil Universitario Nino Jesus
Department Name
Paediatric Haemato-Oncology
Contact Person Name
Alba Rubio San Simón
Contact Person Email
alba.rubio@salud.madrid.org
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Oncology Department
Contact Person Name
Maria Isabel Sevilla Garcia
Contact Person Email
isevilla02@yahoo.es
Site Name
Hospital Universitario De Cruces
Department Name
Paediatric Oncology Department
Contact Person Name
Aizpea Echevarria Varona
Site Name
Hospital Universitario Regional De Malaga
Department Name
Paediatric Oncology Department
Contact Person Name
Guiomar Gutiérrez Schiaffino
Contact Person Email
guiogs@hotmail.com
Site Name
University Hospital Son Espases
Department Name
Paediatric Oncology Department
Contact Person Name
Mikael Lorite Reggiori
Contact Person Email
mikael.lorite@ssib.es
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Oncology Department
Contact Person Name
Javier Martín Broto
Contact Person Email
jmartin@atbsarc.org
Site Name
Hospital Universitario De Canarias (additional site entries aggregated)
Department Name
Oncology / Radiotherapy / Paediatric departments (multiple entries in Spain listing various departments)

Netherlands

Earliest CTIS Part Ii Submission Date
27-06-2025
Latest Decision Or Authorization Date
18-07-2025
Processing Time Days
21
Number Of Sites
2
Number Of Participants
70

Sites

Site Name
Universitair Medisch Centrum Groningen
Department Name
Radiation Oncology
Contact Person Name
John Maduro
Contact Person Email
j.h.maduro@umcg.nl
Site Name
Prinses Maxima Centrum voor Kinderoncologie B.V.
Department Name
Solid Tumours
Contact Person Name
Lianne Haveman

France

Earliest CTIS Part Ii Submission Date
25-06-2025
Latest Decision Or Authorization Date
21-07-2025
Processing Time Days
26
Number Of Sites
39
Number Of Participants
190

Sites

Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Pediatrics
Contact Person Name
Faustine Tardy
Site Name
Centre Francois Baclesse
Department Name
Sarcoma department
Contact Person Name
Sabine Noal
Contact Person Email
s.noal@baclesse.unicancer.fr
Site Name
Institut Curie Paris
Department Name
Adult oncology / Pediatrics (multiple entries)
Contact Person Name
Sarah Winter / Valérie Laurence
Site Name
Centre Hospitalier Universitaire Reims
Department Name
Pediatrics
Contact Person Name
Grégory Guimard
Contact Person Email
gguimard@chu-reims.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Medical oncology
Contact Person Name
Emmanuelle Bompas
Site Name
CHRU de Nancy - Hôpitaux de Brabois
Department Name
Pediatrics
Contact Person Name
Ludovic Mansuy
Contact Person Email
Jl.lemelle@chru-nancy.fr
Site Name
Institut Bergonié
Department Name
Medical oncology
Contact Person Name
Maud Toulmonde
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Pediatrics
Contact Person Name
Morgane Cleirec
Contact Person Email
morgane.cleirec@chu-nantes.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Pediatrics
Contact Person Name
Marie-Dominique Tabone
Contact Person Email
marie-dominique.tabone@aphp.fr
Site Name
Centre Antoine Lacassagne
Department Name
Medical oncology
Contact Person Name
Jérôme Doyen
Contact Person Email
Jerome.DOYEN@nice.unicancer.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Pediatrics
Contact Person Name
Séverine Bobillier Chaumont
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Pediatrics
Contact Person Name
Jamie Probert
Contact Person Email
Jamie.probert@chu-rennes.fr
Site Name
Centre Georges François Leclerc
Department Name
Medical oncology
Contact Person Name
Isabelle Desmoulins
Contact Person Email
emartin@cgfl.fr
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Pediatrics
Contact Person Name
Antoine Gourmel
Contact Person Email
Gourmel.Antoine@chu-amiens.fr
Site Name
CHU de Rouen - Hôpital Charles Nicolle
Department Name
Pediatrics
Contact Person Name
Marie Cardine
Contact Person Email
marie-cardine@chu-rouen.fr
Site Name
Hôpital Côte de Nacre - CHU de Caen
Department Name
Pediatrics
Contact Person Name
Marianna Deparis
Contact Person Email
deparis-m@chu-caen.fr
Site Name
Centre Hospitalier Universitaire De La Reunion
Department Name
Pediatric oncology
Contact Person Name
Stéphanie Gourdon
Site Name
Institut Paoli Calmettes
Department Name
Medical oncology
Contact Person Name
François Bertucci
Contact Person Email
bertuccif@ipc.unicancer.fr
Site Name
ICANS - Institut de cancérologie Strasbourg Europe
Department Name
Radiotherapy
Contact Person Name
Georges Noel
Contact Person Email
g.noel@icans.eu
Site Name
Hôpital Archet 2
Department Name
Pediatrics
Contact Person Name
Joy Benadiba
Contact Person Email
benadiba.j@chu-nice.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Pediatrics
Contact Person Name
Marie-Pierre Castex
Contact Person Email
castex.mp@chu-toulouse.fr
Site Name
Institut de Cancérologie de Lorraine (ICL)
Department Name
Medical oncology
Contact Person Name
Maria Rios
Contact Person Email
m.rios@nancy.unicancer.fr
Site Name
Gustave Roussy
Department Name
Pediatrics
Contact Person Name
Nathalie Gaspar
Site Name
Centre Henri Becquerel
Department Name
Radiotherapy
Contact Person Name
Mihai Levitchi
Site Name
Centre Oscar Lambret
Department Name
Pediatrics
Contact Person Name
Cyril Lervat
Contact Person Email
c-lervat@o-lambret.fr
Site Name
Hôpital de la Timone
Department Name
Adult oncology / Pediatrics (multiple entries)
Contact Person Name
Florence Duffaud / Gabriel Revon-Riviere
Site Name
CHRU Jean Minjoz
Department Name
Pediatrics
Contact Person Name
Sébastien Klein
Contact Person Email
vlaithier@chu-besancon.fr
Site Name
CHU de Montpellier
Department Name
Pediatrics
Contact Person Name
Laure Saumet
Contact Person Email
l-saumet@chu-montpellier.fr
Site Name
Centre Leon Berard
Department Name
Pediatrics
Contact Person Name
Perrine Marec Berard
Contact Person Email
perrine.marec-berard@ihope.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Pediatrics
Contact Person Name
Cécile Verite
Contact Person Email
cecile.verite@chu-bordeaux.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Pediatrics
Contact Person Name
Claire Briandet
Contact Person Email
Claire.briandet@chu-dijon.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Pediatrics
Contact Person Name
Chrystelle Dupraz
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Pediatrics
Contact Person Name
Justyna Kanold
Contact Person Email
jkanold@chu-clermontferrand.fr

Norway

Earliest CTIS Part Ii Submission Date
17-06-2025
Latest Decision Or Authorization Date
17-07-2025
Processing Time Days
30
Number Of Sites
2
Number Of Participants
10

Sites

Site Name
Oslo University Hospital HF
Department Name
Department of Oncology
Contact Person Name
Kjetil Boye
Contact Person Email
pbk@ous-hf.no
Site Name
Oslo University Hospital HF
Department Name
Department of Pediatric Oncology and Hematology
Contact Person Name
Niklas Stabell
Contact Person Email
niksta@ous-hf.no

Sponsor

Primary sponsor

Full Name
The University Of Birmingham
Organisation Type
Educational Institution
Country Of Registered Address
United Kingdom

Third parties

  • {"country":"Netherlands","full_name":"Princess Maxima Center Utrecht","duties_or_roles":"Imaging (radiology) substudies program","organisation_type":"Health care"}
  • {"country":"Belgium","full_name":"European Organisation for Research and Treatment of Cancer","duties_or_roles":"Quartet Imaging program (rtqaQUARTET_INTER-EWING-1)","organisation_type":"Health care / Research organisation"}
  • {"country":"France","full_name":"Aquilab By Coexya","duties_or_roles":"Imaging program (alternative to QUARTET) France only","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Julius Clinical International B.V.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"European Society for Paediatric Oncology","duties_or_roles":"Quartet Imaging program","organisation_type":"Health care / Professional society"}
  • {"country":"United Kingdom","full_name":"The Institute Of Cancer Research","duties_or_roles":"biobank; other (code 4)","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United Kingdom","full_name":"University Of Leeds","duties_or_roles":"biobank; other (code 4)","organisation_type":"Educational Institution"}

Investigational products

Investigational Product Name
VINORELBINE
Active Substance
VINORELBINE
Modality
Small molecule
Routes Of Administration
Oral; Intravenous
Route
Oral; Intravenous
Investigational Product Name
CYCLOPHOSPHAMIDE
Active Substance
CYCLOPHOSPHAMIDE
Modality
Small molecule
Routes Of Administration
Oral; Intravenous
Route
Oral; Intravenous
Combination Treatment
Yes

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