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A Study of Bevacizumab (Avastin) in Combination With Temozolomide (TMZ) and Radiotherapy in Paediatric and Adolescent Participants With High-Grade Glioma

Primary Purpose

High Grade Glioma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Bevacizumab

Radiotherapy

Temozolomide (TMZ)

About this trial

This is an interventional treatment trial for High Grade Glioma

Eligibility Criteria

6 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria - Main cohort :

Paediatric participants, aged >= 3 years and < 18 years
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 - Main cohort:

Metastatic HGG defined as evidence of neuraxis dissemination by MRI or positive cerebrospinal fluid (CSF) cytology
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

Sites / Locations

The Children's Hospital at Westmead
Lady Cilento Children's Hospital; Oncology Services Group, Level 12b
Kepler Universitätskliniken GmbH - Med Campus IV.
Medizinische Universität Wien
UZ Leuven Gasthuisberg
Alberta Children'S Hospital
Hospital For Sick Children
Fakultni nemocnice Brno; 2. detska klinika, pracoviste Detska nemocnice
Fakultni Nemocnice V Motole, S.P.
Skejby Sygehus - Aarhus University Hospital; CF Center, Børneafdeling A
Rigshospitalet; Onkologisk Klinik
Centre Hospitalier d'Angers; Service de cancérologie pédiatrique
CHU ESTAING; Centre Regional de Cancérologie et Thérapie Cellulaire Pédiatrique (CRCTCP)
Centre Oscar Lambret; Service de Pediatrie
Centre Leon Berard
Hopital Timone Enfants; Onco Pediatrie
Hopital Lenval; Service Hématologie Infantile
Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris; Service d Oncologie Pediatrique
CHRU de Rennes - Hôpital Sud- Service d'Hématologie Pédiatrique
Hopital Nord;Consult Pediatrie
Hôpital Hautepierre
Hopital Des Enfants; Service d Hemato-Oncologie
CHRU de Tours - Centre de Pédiatrie Clocheville; Service d'Oncopédiatrie
Hopital Brabois Enfants
Institut Gustave Roussy; Service Pediatrique
Semmelweis University, 2nd Dept of Pediatrics Neurooncology Unit
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh
Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS; U.O.S. Neuroncologia
Fondazione IRCCS Istituto Nazionale dei Tumori
Azienda Ospedaliera di Padova
UMC St Radboud
Erasmus Mc/Sophia's Childrens Hospital; Dept. of Pediatric Oncology
Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii
Hospital Sant Joan De Deu
Hospital Universitari Vall d'Hebron
Hospital Universitario La Fe
Sahlgrenska Universitetssjukhuset, Östra Sjukhus; Drottning Silvias Barnsjukhus
Universitetssjukhuset Linköping; Barn och Ungdomskliniken
Skånes Universitetssjukhus
Karolinska Universitetssjukhuset, Solna; Astrid Lindgrens Barnsjukhus, Barcanceravdelningen
Birmingham Childrens Hospital; Oncology Dept
Bristol Royal Hospital for Children; Paediatric Haematology, Oncology, BMT
Addenbrookes Hospital; Paediatric Oncology Ward C2
Royal Hospital for Sick Children
Leeds General Infirmary; Ward 35
Alder Hey Children's NHS Foundation Trust
University College London NHS Foundation Trust
Great Ormond Street Hospital; Dept. Of Pediatric Oncology
Royal Manchester Childrens Hospital
Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust
Queens Medical Centre
Southampton General Hospital
Royal Marsden Hospital; Pediatric Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Bevacizumab + TMZ Young Patient Cohort (YPC)

Main Cohort: Chemoradiation + Bevacizumab + TMZ

Main Cohort: Chemoradiation + TMZ

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Event-Free Survival (EFS) as Assessed by the Central Radiology Review Committee (CRRC)

EFS was defined as the time from randomisation to the earliest occurrence of any of the following: tumor progression, tumor recurrence, second primary non- HGG malignancy or death attributable to any cause. Tumor assessments were conducted using magnetic resonance imaging (MRI) and reviewed by the site-independent CRRC using Response Assessment in Neuro-Oncology (RANO) criteria. Tumor progression was defined as clear clinical progression or >/= 25% increase in the sum of the products of perpendicular diameters of the contrast enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease was observed) or best response and with the subject on stable or increasing doses of corticosteroids. Tumor recurrence was defined as recurrence after tumor was completely resected (no disease present at baseline). EFS was estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Overall Survival

Overall Survival was defined as the time of diagnosis to the date of death due to any cause. Overall Survival was estimated using the Kaplan-Meier method.

Percentage of Participants With 1-Year Survival

1-year survival was estimated using the Kaplan-Meier method.

Percentage of Participants With EFS as Determined by the CRRC at 6 Months

EFS was defined as the time from randomisation to the earliest occurrence of any of the following: tumor progression, tumor recurrence, second primary non- HGG malignancy or death attributable to any cause. Tumor assessments were conducted using MRI and reviewed by the site-independent CRRC using RANO criteria. Tumor progression was defined as clear clinical progression or >/= 25% increase in the sum of the products of perpendicular diameters of the contrast enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease was observed) or best response and with the subject on stable or increasing doses of corticosteroids. Tumor recurrence was defined as recurrence after tumor was completely resected (no disease present at baseline). EFS was estimated using the Kaplan-Meier method.

Percentage of Participants With EFS as Determined by the CRRC at 1 Year

EFS was defined as the time from randomisation to the earliest occurrence of any of the following: tumor progression, tumor recurrence, second primary non- HGG malignancy or death attributable to any cause. Tumor assessments were conducted using MRI and reviewed by the site-independent CRRC using RANO criteria. Tumor progression was defined as clear clinical progression or >/= 25% increase in the sum of the products of perpendicular diameters of the contrast enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease was observed) or best response and with the subject on stable or increasing doses of corticosteroids. Tumor recurrence was defined as recurrence after tumor was completely resected (no disease present at baseline). EFS was estimated using the Kaplan-Meier method.

EFS as Assessed by the Investigator

EFS was defined as the time from randomisation to the earliest occurrence of any of the following: tumor progression, tumor recurrence, second primary non-HGG malignancy or death attributable to any cause. Tumor assessments were conducted using MRI and reviewed by the investigator using RANO criteria. Tumor progression was defined as clear clinical progression or >/= 25% increase in the sum of the products of perpendicular diameters of the contrast enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease was observed) or best response and with the participant on stable or increasing doses of corticosteroids. Tumor recurrence was defined as recurrence after tumor was completely resected (no disease present at baseline). EFS was estimated using the Kaplan-Meier method.

Objective Response Rate (ORR)

ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) determined on two consecutive occasions >/= 4 weeks apart. Tumor assessments were conducted using MRI and reviewed by the site-independent CRRC using RANO criteria. The following were needed to qualify as CR: complete disappearance of all measurable enhancing lesions sustained for at least 4 weeks by MRI, no steroids above physiological levels, clinical status stable or improved compared to baseline. The following were needed to qualify as PR: ≥ 50% decrease from baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks by MRI, steroid dose not increased compared to baseline, clinical status stable or improved compared to baseline.

Concordance Between Structural Versus Multimodal Imaging for CRRC-Assessed Event-Free Survival

Concordance is presented as the percentage of participants with concordance between assessments. EFS concordance was defined as event Structural assessment and Diffusion Perfusion assessment occurs within 28 days or no event Structural and no Diffusion Perfusion.

Health Status as Measured by the Health Utility Index (HUI)

HUI is a preference-based, multi-attitude, health-related instrument specifically developed for use with children. HUI consists of eight attributes of health status: vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain. Each attribute had 5 or 6 levels varying from highly impaired to normal. Each of the eight health dimensions was tested separately and a composite score ranging between 1 (perfect health) and 0 (death) was obtained for participants aged 5 years or older.

Neurological Psychological Function as Measured by the Wechsler Scale

The Wechsler Intelligence Scale for Children version IV (WISC-IV) was used to generate a full scale intelligence quotient (IQ) which represents a child's general intellectual ability. The average IQ score is 100, with lower scores representing lower intellectual ability.

Percentage of Participants Who Completed >/= 90% of Planned Radiotherapy and TMZ Administrations

Percentage of Participants With a Treatment Delay or Discontinuation

Number of Radiotherapy Dose Administrations in the Concurrent Phase

Number of doses were assessed for the concurrent phase, which is the treatment period after the initial treatment phase and including the subsequent treatment break of approximately 4 weeks.

Number of Dose Administrations of TMZ and Bevacizumab in the Concurrent Phase

Number of doses were assessed for the concurrent phase, which is the treatment period after the initial treatment phase and including the subsequent treatment break of approximately 4 weeks.

Percentage of Participants With an Adverse Event (AE)

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Full Information

NCT ID

NCT01390948

First Posted

July 7, 2011

Last Updated

July 23, 2020

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01390948

Brief Title

A Study of Bevacizumab (Avastin) in Combination With Temozolomide (TMZ) and Radiotherapy in Paediatric and Adolescent Participants With High-Grade Glioma

Official Title

A Phase II Open-Label, Randomized, Multi-Centre Comparative Study Of Bevacizumab-Based Therapy In Paediatric Patients With Newly Diagnosed Supratentorial, Infratentorial Cerebellar, or Peduncular High-Grade Glioma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

October 18, 2011 (Actual)

Primary Completion Date

February 5, 2016 (Actual)

Study Completion Date

January 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This randomized, open-label, multicenter, 2-arm study will investigate the efficacy, safety, tolerability and pharmacokinetics of bevacizumab when added to postoperative radiotherapy with concomitant and adjuvant TMZ as compared to postoperative radiotherapy with concomitant and adjuvant TMZ alone in paediatric participants with newly diagnosed histologically confirmed World Health Organization (WHO) Grade III or IV localized supratentorial or infratentorial cerebellar or peduncular high grade glioma (HGG). Participants will be randomly assigned to one of two treatment arms. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

High Grade Glioma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

124 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bevacizumab + TMZ Young Patient Cohort (YPC)

Arm Type

Experimental

Arm Description

Arm Title

Main Cohort: Chemoradiation + Bevacizumab + TMZ

Arm Type

Experimental

Arm Description

Arm Title

Main Cohort: Chemoradiation + TMZ

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

10 milligrams per kilogram every 2 weeks during the study for up to 12 cycles, each cycle length of 28 days

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

Total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.

Intervention Type

Drug

Intervention Name(s)

Temozolomide (TMZ)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Event-Free Survival (EFS) as Assessed by the Central Radiology Review Committee (CRRC)

Description

Time Frame

From the time of randomization to the date of any defined event (up to 12 months)

Secondary Outcome Measure Information:

Title

Overall Survival

Description

Overall Survival was defined as the time of diagnosis to the date of death due to any cause. Overall Survival was estimated using the Kaplan-Meier method.

Time Frame

From the time of randomization to the date of death (up to approximately 60 months)

Title

Percentage of Participants With 1-Year Survival

Description

1-year survival was estimated using the Kaplan-Meier method.

Time Frame

1 year after end of treatment

Title

Percentage of Participants With EFS as Determined by the CRRC at 6 Months

Description

EFS was defined as the time from randomisation to the earliest occurrence of any of the following: tumor progression, tumor recurrence, second primary non- HGG malignancy or death attributable to any cause. Tumor assessments were conducted using MRI and reviewed by the site-independent CRRC using RANO criteria. Tumor progression was defined as clear clinical progression or >/= 25% increase in the sum of the products of perpendicular diameters of the contrast enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease was observed) or best response and with the subject on stable or increasing doses of corticosteroids. Tumor recurrence was defined as recurrence after tumor was completely resected (no disease present at baseline). EFS was estimated using the Kaplan-Meier method.

Time Frame

6 months

Title

Percentage of Participants With EFS as Determined by the CRRC at 1 Year

Description

EFS was defined as the time from randomisation to the earliest occurrence of any of the following: tumor progression, tumor recurrence, second primary non- HGG malignancy or death attributable to any cause. Tumor assessments were conducted using MRI and reviewed by the site-independent CRRC using RANO criteria. Tumor progression was defined as clear clinical progression or >/= 25% increase in the sum of the products of perpendicular diameters of the contrast enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease was observed) or best response and with the subject on stable or increasing doses of corticosteroids. Tumor recurrence was defined as recurrence after tumor was completely resected (no disease present at baseline). EFS was estimated using the Kaplan-Meier method.

Time Frame

1 year

Title

EFS as Assessed by the Investigator

Description

EFS was defined as the time from randomisation to the earliest occurrence of any of the following: tumor progression, tumor recurrence, second primary non-HGG malignancy or death attributable to any cause. Tumor assessments were conducted using MRI and reviewed by the investigator using RANO criteria. Tumor progression was defined as clear clinical progression or >/= 25% increase in the sum of the products of perpendicular diameters of the contrast enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease was observed) or best response and with the participant on stable or increasing doses of corticosteroids. Tumor recurrence was defined as recurrence after tumor was completely resected (no disease present at baseline). EFS was estimated using the Kaplan-Meier method.

Time Frame

From the time of randomization to the date of any defined event (up to 12 months)

Title

Objective Response Rate (ORR)

Description

Time Frame

From the time of randomization to the date of any defined event (up to 12 months)

Title

Concordance Between Structural Versus Multimodal Imaging for CRRC-Assessed Event-Free Survival

Description

Time Frame

Up to 12 months

Title

Health Status as Measured by the Health Utility Index (HUI)

Description

Time Frame

Baseline, Cycle 6 of the adjuvant phase, end of treatment (approximately 58 weeks post-baseline), and yearly during the follow-up period (maximum 5 years in follow-up)

Title

Neurological Psychological Function as Measured by the Wechsler Scale

Description

Time Frame

End of treatment (approximately 58 weeks post-baseline)

Title

Percentage of Participants Who Completed >/= 90% of Planned Radiotherapy and TMZ Administrations

Time Frame

From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)

Title

Percentage of Participants With a Treatment Delay or Discontinuation

Time Frame

From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)

Title

Number of Radiotherapy Dose Administrations in the Concurrent Phase

Description

Number of doses were assessed for the concurrent phase, which is the treatment period after the initial treatment phase and including the subsequent treatment break of approximately 4 weeks.

Time Frame

Beginning of the concurrent phase to end of treatment break (10 weeks)

Title

Number of Dose Administrations of TMZ and Bevacizumab in the Concurrent Phase

Description

Number of doses were assessed for the concurrent phase, which is the treatment period after the initial treatment phase and including the subsequent treatment break of approximately 4 weeks.

Time Frame

Beginning of the concurrent phase to end of treatment break (10 weeks)

Title

Percentage of Participants With an Adverse Event (AE)

Description

Time Frame

From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria - Main cohort : Paediatric participants, aged >= 3 years and < 18 years 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 - Main cohort: Metastatic HGG defined as evidence of neuraxis dissemination by MRI or positive cerebrospinal fluid (CSF) cytology 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

The Children's Hospital at Westmead

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Facility Name

Lady Cilento Children's Hospital; Oncology Services Group, Level 12b

City

South Brisbane

State/Province

Queensland

ZIP/Postal Code

QLD 4101

Country

Australia

Facility Name

Kepler Universitätskliniken GmbH - Med Campus IV.

City

Linz

ZIP/Postal Code

4020

Country

Austria

Facility Name

Medizinische Universität Wien

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

UZ Leuven Gasthuisberg

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Alberta Children'S Hospital

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T3B 6A8

Country

Canada

Facility Name

Hospital For Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X8

Country

Canada

Facility Name

Fakultni nemocnice Brno; 2. detska klinika, pracoviste Detska nemocnice

City

Brno

ZIP/Postal Code

62500

Country

Czechia

Facility Name

Fakultni Nemocnice V Motole, S.P.

City

Prague

ZIP/Postal Code

15060

Country

Czechia

Facility Name

Skejby Sygehus - Aarhus University Hospital; CF Center, Børneafdeling A

City

Aarhus N

ZIP/Postal Code

8200

Country

Denmark

Facility Name

Rigshospitalet; Onkologisk Klinik

City

København Ø

ZIP/Postal Code

2100

Country

Denmark

Facility Name

Centre Hospitalier d'Angers; Service de cancérologie pédiatrique

City

Angers

ZIP/Postal Code

49033

Country

France

Facility Name

CHU ESTAING; Centre Regional de Cancérologie et Thérapie Cellulaire Pédiatrique (CRCTCP)

City

Clermont Ferrand

ZIP/Postal Code

63003

Country

France

Facility Name

Centre Oscar Lambret; Service de Pediatrie

City

Lille

ZIP/Postal Code

59020

Country

France

Facility Name

Centre Leon Berard

City

Lyon

ZIP/Postal Code

69008

Country

France

Facility Name

Hopital Timone Enfants; Onco Pediatrie

City

Marseille

ZIP/Postal Code

13385

Country

France

Facility Name

Hopital Lenval; Service Hématologie Infantile

City

Nice

ZIP/Postal Code

06200

Country

France

Facility Name

Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris; Service d Oncologie Pediatrique

City

Paris

ZIP/Postal Code

75248

Country

France

Facility Name

CHRU de Rennes - Hôpital Sud- Service d'Hématologie Pédiatrique

City

Rennes

ZIP/Postal Code

35056

Country

France

Facility Name

Hopital Nord;Consult Pediatrie

City

St Priest En Jarez

ZIP/Postal Code

42777

Country

France

Facility Name

Hôpital Hautepierre

City

Strasbourg

ZIP/Postal Code

67200

Country

France

Facility Name

Hopital Des Enfants; Service d Hemato-Oncologie

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

CHRU de Tours - Centre de Pédiatrie Clocheville; Service d'Oncopédiatrie

City

Tours

ZIP/Postal Code

37044

Country

France

Facility Name

Hopital Brabois Enfants

City

Vandoeuvre-les-Nancy cedex

ZIP/Postal Code

54511

Country

France

Facility Name

Institut Gustave Roussy; Service Pediatrique

City

Villejuif

ZIP/Postal Code

94805

Country

France

Facility Name

Semmelweis University, 2nd Dept of Pediatrics Neurooncology Unit

City

Budapest

ZIP/Postal Code

1094

Country

Hungary

Facility Name

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh

City

Bologna

State/Province

Emilia-Romagna

ZIP/Postal Code

40138

Country

Italy

Facility Name

Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS; U.O.S. Neuroncologia

City

Genova

State/Province

Liguria

ZIP/Postal Code

16147

Country

Italy

Facility Name

Fondazione IRCCS Istituto Nazionale dei Tumori

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20133

Country

Italy

Facility Name

Azienda Ospedaliera di Padova

City

Padova

State/Province

Veneto

ZIP/Postal Code

35128

Country

Italy

Facility Name

UMC St Radboud

City

Nijmegen

ZIP/Postal Code

6525 GA

Country

Netherlands

Facility Name

Erasmus Mc/Sophia's Childrens Hospital; Dept. of Pediatric Oncology

City

Rotterdam

ZIP/Postal Code

3015 GJ

Country

Netherlands

Facility Name

Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii

City

Warsaw

ZIP/Postal Code

04-746

Country

Poland

Facility Name

Hospital Sant Joan De Deu

City

Esplugues De Llobregas

State/Province

Barcelona

ZIP/Postal Code

08950

Country

Spain

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Universitario La Fe

City

Valencia

ZIP/Postal Code

46014

Country

Spain

Facility Name

Sahlgrenska Universitetssjukhuset, Östra Sjukhus; Drottning Silvias Barnsjukhus

City

Göteborg

ZIP/Postal Code

416 85

Country

Sweden

Facility Name

Universitetssjukhuset Linköping; Barn och Ungdomskliniken

City

Linkoeping

ZIP/Postal Code

581 85

Country

Sweden

Facility Name

Skånes Universitetssjukhus

City

Lund

ZIP/Postal Code

221 85

Country

Sweden

Facility Name

Karolinska Universitetssjukhuset, Solna; Astrid Lindgrens Barnsjukhus, Barcanceravdelningen

City

Solna

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

Birmingham Childrens Hospital; Oncology Dept

City

Birmingham

ZIP/Postal Code

B4 6NH

Country

United Kingdom

Facility Name

Bristol Royal Hospital for Children; Paediatric Haematology, Oncology, BMT

City

Bristol

ZIP/Postal Code

BS2 8BJ

Country

United Kingdom

Facility Name

Addenbrookes Hospital; Paediatric Oncology Ward C2

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Facility Name

Royal Hospital for Sick Children

City

Edinburgh

ZIP/Postal Code

EH91LF

Country

United Kingdom

Facility Name

Leeds General Infirmary; Ward 35

City

Leeds

ZIP/Postal Code

LS1 3EX

Country

United Kingdom

Facility Name

Alder Hey Children's NHS Foundation Trust

City

Liverpool

ZIP/Postal Code

L12 2AP

Country

United Kingdom

Facility Name

University College London NHS Foundation Trust

City

London

ZIP/Postal Code

NW1 2PG

Country

United Kingdom

Facility Name

Great Ormond Street Hospital; Dept. Of Pediatric Oncology

City

London

ZIP/Postal Code

WC1N 3JH

Country

United Kingdom

Facility Name

Royal Manchester Childrens Hospital

City

Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

Facility Name

Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust

City

Newcastle upon Tyne

ZIP/Postal Code

NE1 4LP

Country

United Kingdom

Facility Name

Queens Medical Centre

City

Nottingham

ZIP/Postal Code

NG7 2UH

Country

United Kingdom

Facility Name

Southampton General Hospital

City

Southampton

ZIP/Postal Code

SO16 6YD

Country

United Kingdom

Facility Name

Royal Marsden Hospital; Pediatric Unit

City

Surrey

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35412366

Citation

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.

Results Reference

derived

PubMed Identifier

31419298

Citation

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.

Results Reference

derived

PubMed Identifier

30819765

Citation

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.

Results Reference

derived

PubMed Identifier

29763623

Citation

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.

Results Reference

derived

PubMed Identifier

29412784

Citation

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.

Results Reference

derived

Learn more about this trial

A Study of Bevacizumab (Avastin) in Combination With Temozolomide (TMZ) and Radiotherapy in Paediatric and Adolescent Participants With High-Grade Glioma

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