A Study of Bevacizumab (Avastin) in Combination With Temozolomide (TMZ) and Radiotherapy in Paediatric and Adolescent Participants With High-Grade Glioma
NCT ID: NCT01390948
Last Updated: 2020-08-06
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
124 participants
INTERVENTIONAL
2011-10-18
2020-01-29
Brief Summary
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Upon approval by the Health Authorities/Ethics Committees in the participating countries, an additional young participant cohort (YPC) (children \>/= 6 months and \< 3 years of age with progressive or relapsed metastatic or localized, supra- or infratentorial, non-brain stem WHO Grade III or IV HGG) was included in the study. Children in the YPC will receive bevacizumab and TMZ without radiation therapy. The anticipated time on study treatment is over 1 year.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Bevacizumab + TMZ Young Patient Cohort (YPC)
Participants aged greater than or equal to (\>/=) 6 months and less than (\<) 3 years will receive 10 milligrams per kilogram (mg/kg) Bevacizumab every 2 weeks and 150 to 200 milligrams per meter squared (mg/m\^2) of TMZ daily on Days 1-5 of each cycle. TMZ will be given at a dose of 150 mg/m\^2 on Days 1-5 of cycle 1 and then escalated to 200 mg/m\^2 on days 1-5 from cycle 2 onwards depending on the tolerance during the 1st cycle.
Bevacizumab
10 milligrams per kilogram every 2 weeks during the study for up to 12 cycles, each cycle length of 28 days
Temozolomide (TMZ)
75 milligrams per square meter (mg/m\^2) daily continuous starting concomitantly with the first radiation fraction and ending with the last radiation fraction for a maximum number of treatment days = 49 days. During the TMZ adjuvant treatment phase and for participants from YPC: TMZ (150 to 200 mg/m\^2/day) x 12 cycles, 1st cycle 150 mg/m\^2/days 1-5, escalated to 200 mg/m\^2 on Days 1-5 from Cycle 2 onwards depending on the tolerance during the 1st cycle. Cycle length = 28 days.
Main Cohort: Chemoradiation + Bevacizumab + TMZ
Participants will receive a total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks with 75 mg/m\^2 TMZ daily for up to 49 days followed by a treatment break of approximately 4 weeks. The treatment break will be followed by an adjuvant treatment phase where participants will receive 150 to 200 mg/m\^2 of TMZ daily on Days 1-5 of each cycle. TMZ will be given at a dose of 150 mg/m\^2 on Days 1-5 of cycle 1 and then escalated to 200 mg/m\^2 on days 1-5 from cycle 2 onwards depending on the tolerance during the 1st cycle. Bevacizumab will be given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period.
Bevacizumab
10 milligrams per kilogram every 2 weeks during the study for up to 12 cycles, each cycle length of 28 days
Radiotherapy
Total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.
Temozolomide (TMZ)
75 milligrams per square meter (mg/m\^2) daily continuous starting concomitantly with the first radiation fraction and ending with the last radiation fraction for a maximum number of treatment days = 49 days. During the TMZ adjuvant treatment phase and for participants from YPC: TMZ (150 to 200 mg/m\^2/day) x 12 cycles, 1st cycle 150 mg/m\^2/days 1-5, escalated to 200 mg/m\^2 on Days 1-5 from Cycle 2 onwards depending on the tolerance during the 1st cycle. Cycle length = 28 days.
Main Cohort: Chemoradiation + TMZ
Participants will receive a total dose of 54 Gy units delivered in 30 daily fractions of 1.8 Gy over 6 weeks with 75 mg/m\^2 TMZ daily for up to 49 days followed by a treatment break of approximately 4 weeks. The treatment break will be followed by an adjuvant treatment phase where participants will receive 150 to 200 mg/m\^2 of TMZ daily on Days 1-5 of each cycle. TMZ will be given at a dose of 150 mg/m\^2 on Days 1-5 of cycle 1 and then escalated to 200 mg/m\^2 on days 1-5 from cycle 2 onwards depending on the tolerance during the 1st cycle.
Radiotherapy
Total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.
Temozolomide (TMZ)
75 milligrams per square meter (mg/m\^2) daily continuous starting concomitantly with the first radiation fraction and ending with the last radiation fraction for a maximum number of treatment days = 49 days. During the TMZ adjuvant treatment phase and for participants from YPC: TMZ (150 to 200 mg/m\^2/day) x 12 cycles, 1st cycle 150 mg/m\^2/days 1-5, escalated to 200 mg/m\^2 on Days 1-5 from Cycle 2 onwards depending on the tolerance during the 1st cycle. Cycle length = 28 days.
Interventions
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Bevacizumab
10 milligrams per kilogram every 2 weeks during the study for up to 12 cycles, each cycle length of 28 days
Radiotherapy
Total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.
Temozolomide (TMZ)
75 milligrams per square meter (mg/m\^2) daily continuous starting concomitantly with the first radiation fraction and ending with the last radiation fraction for a maximum number of treatment days = 49 days. During the TMZ adjuvant treatment phase and for participants from YPC: TMZ (150 to 200 mg/m\^2/day) x 12 cycles, 1st cycle 150 mg/m\^2/days 1-5, escalated to 200 mg/m\^2 on Days 1-5 from Cycle 2 onwards depending on the tolerance during the 1st cycle. Cycle length = 28 days.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Written informed consent obtained from the participant/parents or legally acceptable representative
* Newly diagnosed localised, supratentorial or infratentorial cerebellar or peduncular, WHO Grade III or IV gliomas
* Local histological diagnosis confirmed by a designated central reference neuropathologist
* Availability of the baseline magnetic resonance imaging (MRI) performed according to imaging guidelines
* Able to commence trial treatment not before 4 weeks after cranial surgery and no later than 6 weeks following the last major surgery
* Adequate bone marrow, coagulation, liver, and renal function
Young Participant Cohort
* Written informed consent obtained from parents or legal representative
* Age at enrollment: from \>= 6 months to \< 3 years of age
* Progressive or relapsed metastatic or localised, supra- or infratentorial, non-brain stem WHO Grade III or IV glioma (local pathology confirmation made either at initial diagnosis or at relapse)
* Availability of a baseline MRI performed according to imaging guidelines
* Adequate organ function (bone marrow, coagulation, liver, kidney)
Exclusion Criteria
* WHO-defined Gliomatosis cerebri (multifocal HGG)
* Any disease or condition that contraindicates the use of the study medication/treatment or places the patient at an unacceptable risk of experiencing treatment-related complications
* Radiological evidence of surgically related intracranial bleeding
* Prior diagnosis of a malignancy and disease-free for 5 years
* Prior systemic anti-cancer therapy
* Previous cranial irradiation
Young Participant Cohort
* WHO-defined Gliomatosis cerebri (multifocal HGG)
* Newly diagnosed HGG below the age of 3 years
* Relapsed HGG below the age of 6 months or above the age of 3 years regardless of the age at first onset
* Indication for concomitant cranial irradiation, regardless of age
* Any disease or condition that contraindicates the use of the study medication/treatment or places the child at an unacceptable risk of experiencing treatment-related complications
* Any specific contraindication to MRI
6 Months
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Lady Cilento Children's Hospital; Oncology Services Group, Level 12b
South Brisbane, Queensland, Australia
Kepler Universitätskliniken GmbH - Med Campus IV.
Linz, , Austria
Medizinische Universität Wien
Vienna, , Austria
UZ Leuven Gasthuisberg
Leuven, , Belgium
Alberta Children'S Hospital
Calgary, Alberta, Canada
Hospital For Sick Children
Toronto, Ontario, Canada
Fakultni nemocnice Brno; 2. detska klinika, pracoviste Detska nemocnice
Brno, , Czechia
Fakultni Nemocnice V Motole, S.P.
Prague, , Czechia
Skejby Sygehus - Aarhus University Hospital; CF Center, Børneafdeling A
Aarhus N, , Denmark
Rigshospitalet; Onkologisk Klinik
København Ø, , Denmark
Centre Hospitalier d'Angers; Service de cancérologie pédiatrique
Angers, , France
CHU ESTAING; Centre Regional de Cancérologie et Thérapie Cellulaire Pédiatrique (CRCTCP)
Clermont-Ferrand, , France
Centre Oscar Lambret; Service de Pediatrie
Lille, , France
Centre Leon Berard
Lyon, , France
Hopital Timone Enfants; Onco Pediatrie
Marseille, , France
Hopital Lenval; Service Hématologie Infantile
Nice, , France
Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris; Service d Oncologie Pediatrique
Paris, , France
CHRU de Rennes - Hôpital Sud- Service d'Hématologie Pédiatrique
Rennes, , France
Hopital Nord;Consult Pediatrie
Saint-Priest-en-Jarez, , France
Hôpital Hautepierre
Strasbourg, , France
Hopital Des Enfants; Service d Hemato-Oncologie
Toulouse, , France
CHRU de Tours - Centre de Pédiatrie Clocheville; Service d'Oncopédiatrie
Tours, , France
Hopital Brabois Enfants
Vandœuvre-lès-Nancy, , France
Institut Gustave Roussy; Service Pediatrique
Villejuif, , France
Semmelweis University, 2nd Dept of Pediatrics Neurooncology Unit
Budapest, , Hungary
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh
Bologna, Emilia-Romagna, Italy
Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS; U.O.S. Neuroncologia
Genoa, Liguria, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, Italy
Azienda Ospedaliera di Padova
Padua, Veneto, Italy
UMC St Radboud
Nijmegen, , Netherlands
Erasmus Mc/Sophia's Childrens Hospital; Dept. of Pediatric Oncology
Rotterdam, , Netherlands
Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii
Warsaw, , Poland
Hospital Sant Joan De Deu
Esplugues de Llobregas, Barcelona, Spain
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital Universitario La Fe
Valencia, , Spain
Sahlgrenska Universitetssjukhuset, Östra Sjukhus; Drottning Silvias Barnsjukhus
Gothenburg, , Sweden
Universitetssjukhuset Linköping; Barn och Ungdomskliniken
Linköping, , Sweden
Skånes Universitetssjukhus
Lund, , Sweden
Karolinska Universitetssjukhuset, Solna; Astrid Lindgrens Barnsjukhus, Barcanceravdelningen
Solna, , Sweden
Birmingham Childrens Hospital; Oncology Dept
Birmingham, , United Kingdom
Bristol Royal Hospital for Children; Paediatric Haematology, Oncology, BMT
Bristol, , United Kingdom
Addenbrookes Hospital; Paediatric Oncology Ward C2
Cambridge, , United Kingdom
Royal Hospital for Sick Children
Edinburgh, , United Kingdom
Leeds General Infirmary; Ward 35
Leeds, , United Kingdom
Alder Hey Children's NHS Foundation Trust
Liverpool, , United Kingdom
University College London NHS Foundation Trust
London, , United Kingdom
Great Ormond Street Hospital; Dept. Of Pediatric Oncology
London, , United Kingdom
Royal Manchester Childrens Hospital
Manchester, , United Kingdom
Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, , United Kingdom
Queens Medical Centre
Nottingham, , United Kingdom
Southampton General Hospital
Southampton, , United Kingdom
Royal Marsden Hospital; Pediatric Unit
Surrey, , United Kingdom
Countries
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References
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Rodriguez D, Calmon R, Aliaga ES, Warren D, Warmuth-Metz M, Jones C, Mackay A, Varlet P, Le Deley MC, Hargrave D, Canete A, Massimino M, Azizi AA, Saran F, Zahlmann G, Garcia J, Vassal G, Grill J, Peet A, Dineen RA, Morgan PS, Jaspan T. MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial. Radiology. 2022 Jul;304(1):174-182. doi: 10.1148/radiol.211464. Epub 2022 Apr 12.
Varlet P, Le Teuff G, Le Deley MC, Giangaspero F, Haberler C, Jacques TS, Figarella-Branger D, Pietsch T, Andreiuolo F, Deroulers C, Jaspan T, Jones C, Grill J. WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial. Neuro Oncol. 2020 Jan 11;22(1):116-127. doi: 10.1093/neuonc/noz142.
Rodriguez D, Chambers T, Warmuth-Metz M, Aliaga ES, Warren D, Calmon R, Hargrave D, Garcia J, Vassal G, Grill J, Zahlmann G, Morgan PS, Jaspan T. Evaluation of the Implementation of the Response Assessment in Neuro-Oncology Criteria in the HERBY Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas. AJNR Am J Neuroradiol. 2019 Mar;40(3):568-575. doi: 10.3174/ajnr.A5982. Epub 2019 Feb 28.
Mackay A, Burford A, Molinari V, Jones DTW, Izquierdo E, Brouwer-Visser J, Giangaspero F, Haberler C, Pietsch T, Jacques TS, Figarella-Branger D, Rodriguez D, Morgan PS, Raman P, Waanders AJ, Resnick AC, Massimino M, Garre ML, Smith H, Capper D, Pfister SM, Wurdinger T, Tam R, Garcia J, Thakur MD, Vassal G, Grill J, Jaspan T, Varlet P, Jones C. Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial. Cancer Cell. 2018 May 14;33(5):829-842.e5. doi: 10.1016/j.ccell.2018.04.004.
Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Canete A, Saran F, Le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G. Phase II, Open-Label, Randomized, Multicenter Trial (HERBY) of Bevacizumab in Pediatric Patients With Newly Diagnosed High-Grade Glioma. J Clin Oncol. 2018 Apr 1;36(10):951-958. doi: 10.1200/JCO.2017.76.0611. Epub 2018 Feb 7.
Other Identifiers
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2010-022189-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ITCC-019
Identifier Type: OTHER
Identifier Source: secondary_id
HGG-01
Identifier Type: OTHER
Identifier Source: secondary_id
BO25041
Identifier Type: -
Identifier Source: org_study_id
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