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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01390948




Registration number
NCT01390948
Ethics application status
Date submitted
7/07/2011
Date registered
11/07/2011
Date last updated
6/08/2020

Titles & IDs
Public title
A Study of Bevacizumab (Avastin) in Combination With Temozolomide (TMZ) and Radiotherapy in Paediatric and Adolescent Participants With High-Grade Glioma
Scientific 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
Secondary ID [1] 0 0
2010-022189-28
Secondary ID [2] 0 0
BO25041
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High Grade Glioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bevacizumab
Treatment: Other - Radiotherapy
Treatment: Drugs - Temozolomide (TMZ)

Experimental: 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.

Experimental: 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.

Active comparator: 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.


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

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

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS) as Assessed by the Central Radiology Review Committee (CRRC)
Timepoint [1] 0 0
From the time of randomization to the date of any defined event (up to 12 months)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From the time of randomization to the date of death (up to approximately 60 months)
Secondary outcome [2] 0 0
Percentage of Participants With 1-Year Survival
Timepoint [2] 0 0
1 year after end of treatment
Secondary outcome [3] 0 0
Percentage of Participants With EFS as Determined by the CRRC at 6 Months
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Percentage of Participants With EFS as Determined by the CRRC at 1 Year
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
EFS as Assessed by the Investigator
Timepoint [5] 0 0
From the time of randomization to the date of any defined event (up to 12 months)
Secondary outcome [6] 0 0
Objective Response Rate (ORR)
Timepoint [6] 0 0
From the time of randomization to the date of any defined event (up to 12 months)
Secondary outcome [7] 0 0
Concordance Between Structural Versus Multimodal Imaging for CRRC-Assessed Event-Free Survival
Timepoint [7] 0 0
Up to 12 months
Secondary outcome [8] 0 0
Health Status as Measured by the Health Utility Index (HUI)
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Neurological Psychological Function as Measured by the Wechsler Scale
Timepoint [9] 0 0
End of treatment (approximately 58 weeks post-baseline)
Secondary outcome [10] 0 0
Percentage of Participants Who Completed >/= 90% of Planned Radiotherapy and TMZ Administrations
Timepoint [10] 0 0
From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)
Secondary outcome [11] 0 0
Percentage of Participants With a Treatment Delay or Discontinuation
Timepoint [11] 0 0
From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)
Secondary outcome [12] 0 0
Number of Radiotherapy Dose Administrations in the Concurrent Phase
Timepoint [12] 0 0
Beginning of the concurrent phase to end of treatment break (10 weeks)
Secondary outcome [13] 0 0
Number of Dose Administrations of TMZ and Bevacizumab in the Concurrent Phase
Timepoint [13] 0 0
Beginning of the concurrent phase to end of treatment break (10 weeks)
Secondary outcome [14] 0 0
Percentage of Participants With an Adverse Event (AE)
Timepoint [14] 0 0
From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)

Eligibility
Key inclusion 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)
Minimum age
6 Months
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Lady Cilento Children's Hospital; Oncology Services Group, Level 12b - South Brisbane
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
QLD 4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Linz
Country [2] 0 0
Austria
State/province [2] 0 0
Wien
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Canada
State/province [4] 0 0
Alberta
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Prague
Country [8] 0 0
Denmark
State/province [8] 0 0
Aarhus N
Country [9] 0 0
Denmark
State/province [9] 0 0
København Ø
Country [10] 0 0
France
State/province [10] 0 0
Angers
Country [11] 0 0
France
State/province [11] 0 0
Clermont Ferrand
Country [12] 0 0
France
State/province [12] 0 0
Lille
Country [13] 0 0
France
State/province [13] 0 0
Lyon
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Nice
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Rennes
Country [18] 0 0
France
State/province [18] 0 0
St Priest En Jarez
Country [19] 0 0
France
State/province [19] 0 0
Strasbourg
Country [20] 0 0
France
State/province [20] 0 0
Toulouse
Country [21] 0 0
France
State/province [21] 0 0
Tours
Country [22] 0 0
France
State/province [22] 0 0
Vandoeuvre-les-Nancy cedex
Country [23] 0 0
France
State/province [23] 0 0
Villejuif
Country [24] 0 0
Hungary
State/province [24] 0 0
Budapest
Country [25] 0 0
Italy
State/province [25] 0 0
Emilia-Romagna
Country [26] 0 0
Italy
State/province [26] 0 0
Liguria
Country [27] 0 0
Italy
State/province [27] 0 0
Lombardia
Country [28] 0 0
Italy
State/province [28] 0 0
Veneto
Country [29] 0 0
Netherlands
State/province [29] 0 0
Nijmegen
Country [30] 0 0
Netherlands
State/province [30] 0 0
Rotterdam
Country [31] 0 0
Poland
State/province [31] 0 0
Warsaw
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Valencia
Country [34] 0 0
Sweden
State/province [34] 0 0
Göteborg
Country [35] 0 0
Sweden
State/province [35] 0 0
Linkoeping
Country [36] 0 0
Sweden
State/province [36] 0 0
Lund
Country [37] 0 0
Sweden
State/province [37] 0 0
Solna
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Birmingham
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Bristol
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Cambridge
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Edinburgh
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Leeds
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Liverpool
Country [44] 0 0
United Kingdom
State/province [44] 0 0
London
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Manchester
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Newcastle upon Tyne
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Nottingham
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Southampton
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.