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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
18/10/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/01/2020
Sample size
Target
Accrual to date
Final
124
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.

Results are available at https://clinicaltrials.gov/study/NCT01390948