A Study of Bevacizumab (Avastin) in Combination With Temozolomide (TMZ) and Radiotherapy in Paediatric and Adolescent Participants With High-Grade Glioma
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01390948
Collaborator
(none)
124
53
3
99.4
2.3
0
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
124 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Oct 18, 2011
Actual Primary Completion Date
:
Feb 5, 2016
Actual Study Completion Date
:
Jan 29, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: Bevacizumab
10 milligrams per kilogram every 2 weeks during the study for up to 12 cycles, each cycle length of 28 days
Other Names:
Drug: 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.
|
| 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. |
Drug: Bevacizumab
10 milligrams per kilogram every 2 weeks during the study for up to 12 cycles, each cycle length of 28 days
Other Names:
Radiation: Radiotherapy
Total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.
Drug: 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.
|
| 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. |
Radiation: Radiotherapy
Total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.
Drug: 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.
|
Outcome Measures
Primary Outcome Measures
- Event-Free Survival (EFS) as Assessed by the Central Radiology Review Committee (CRRC) [From the time of randomization to the date of any defined event (up to 12 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 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 [From the time of randomization to the date of death (up to approximately 60 months)]
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 after end of treatment]
1-year survival was estimated using the Kaplan-Meier method.
- Percentage of Participants With EFS as Determined by the CRRC at 6 Months [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 [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 [From the time of randomization to the date of any defined event (up to 12 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 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) [From the time of randomization to the date of any defined event (up to 12 months)]
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 [Up to 12 months]
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) [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)]
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 [End of treatment (approximately 58 weeks post-baseline)]
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 [From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)]
- Percentage of Participants With a Treatment Delay or Discontinuation [From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)]
- Number of Radiotherapy Dose Administrations in the Concurrent Phase [Beginning of the concurrent phase to end of treatment break (10 weeks)]
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 [Beginning of the concurrent phase to end of treatment break (10 weeks)]
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) [From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Months
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Children's Hospital at Westmead | Westmead | New South Wales | Australia | 2145 |
| 2 | Lady Cilento Children's Hospital; Oncology Services Group, Level 12b | South Brisbane | Queensland | Australia | QLD 4101 |
| 3 | Kepler Universitätskliniken GmbH - Med Campus IV. | Linz | Austria | 4020 | |
| 4 | Medizinische Universität Wien | Wien | Austria | 1090 | |
| 5 | UZ Leuven Gasthuisberg | Leuven | Belgium | 3000 | |
| 6 | Alberta Children'S Hospital | Calgary | Alberta | Canada | T3B 6A8 |
| 7 | Hospital For Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
| 8 | Fakultni nemocnice Brno; 2. detska klinika, pracoviste Detska nemocnice | Brno | Czechia | 62500 | |
| 9 | Fakultni Nemocnice V Motole, S.P. | Prague | Czechia | 15060 | |
| 10 | Skejby Sygehus - Aarhus University Hospital; CF Center, Børneafdeling A | Aarhus N | Denmark | 8200 | |
| 11 | Rigshospitalet; Onkologisk Klinik | København Ø | Denmark | 2100 | |
| 12 | Centre Hospitalier d'Angers; Service de cancérologie pédiatrique | Angers | France | 49033 | |
| 13 | CHU ESTAING; Centre Regional de Cancérologie et Thérapie Cellulaire Pédiatrique (CRCTCP) | Clermont Ferrand | France | 63003 | |
| 14 | Centre Oscar Lambret; Service de Pediatrie | Lille | France | 59020 | |
| 15 | Centre Leon Berard | Lyon | France | 69008 | |
| 16 | Hopital Timone Enfants; Onco Pediatrie | Marseille | France | 13385 | |
| 17 | Hopital Lenval; Service Hématologie Infantile | Nice | France | 06200 | |
| 18 | Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris; Service d Oncologie Pediatrique | Paris | France | 75248 | |
| 19 | CHRU de Rennes - Hôpital Sud- Service d'Hématologie Pédiatrique | Rennes | France | 35056 | |
| 20 | Hopital Nord;Consult Pediatrie | St Priest En Jarez | France | 42777 | |
| 21 | Hôpital Hautepierre | Strasbourg | France | 67200 | |
| 22 | Hopital Des Enfants; Service d Hemato-Oncologie | Toulouse | France | 31059 | |
| 23 | CHRU de Tours - Centre de Pédiatrie Clocheville; Service d'Oncopédiatrie | Tours | France | 37044 | |
| 24 | Hopital Brabois Enfants | Vandoeuvre-les-Nancy cedex | France | 54511 | |
| 25 | Institut Gustave Roussy; Service Pediatrique | Villejuif | France | 94805 | |
| 26 | Semmelweis University, 2nd Dept of Pediatrics Neurooncology Unit | Budapest | Hungary | 1094 | |
| 27 | Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh | Bologna | Emilia-Romagna | Italy | 40138 |
| 28 | Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS; U.O.S. Neuroncologia | Genova | Liguria | Italy | 16147 |
| 29 | Fondazione IRCCS Istituto Nazionale dei Tumori | Milano | Lombardia | Italy | 20133 |
| 30 | Azienda Ospedaliera di Padova | Padova | Veneto | Italy | 35128 |
| 31 | UMC St Radboud | Nijmegen | Netherlands | 6525 GA | |
| 32 | Erasmus Mc/Sophia's Childrens Hospital; Dept. of Pediatric Oncology | Rotterdam | Netherlands | 3015 GJ | |
| 33 | Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii | Warsaw | Poland | 04-746 | |
| 34 | Hospital Sant Joan De Deu | Esplugues De Llobregas | Barcelona | Spain | 08950 |
| 35 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | 08035 | |
| 36 | Hospital Universitario La Fe | Valencia | Spain | 46014 | |
| 37 | Sahlgrenska Universitetssjukhuset, Östra Sjukhus; Drottning Silvias Barnsjukhus | Göteborg | Sweden | 416 85 | |
| 38 | Universitetssjukhuset Linköping; Barn och Ungdomskliniken | Linkoeping | Sweden | 581 85 | |
| 39 | Skånes Universitetssjukhus | Lund | Sweden | 221 85 | |
| 40 | Karolinska Universitetssjukhuset, Solna; Astrid Lindgrens Barnsjukhus, Barcanceravdelningen | Solna | Sweden | 171 76 | |
| 41 | Birmingham Childrens Hospital; Oncology Dept | Birmingham | United Kingdom | B4 6NH | |
| 42 | Bristol Royal Hospital for Children; Paediatric Haematology, Oncology, BMT | Bristol | United Kingdom | BS2 8BJ | |
| 43 | Addenbrookes Hospital; Paediatric Oncology Ward C2 | Cambridge | United Kingdom | CB2 0QQ | |
| 44 | Royal Hospital for Sick Children | Edinburgh | United Kingdom | EH91LF | |
| 45 | Leeds General Infirmary; Ward 35 | Leeds | United Kingdom | LS1 3EX | |
| 46 | Alder Hey Children's NHS Foundation Trust | Liverpool | United Kingdom | L12 2AP | |
| 47 | University College London NHS Foundation Trust | London | United Kingdom | NW1 2PG | |
| 48 | Great Ormond Street Hospital; Dept. Of Pediatric Oncology | London | United Kingdom | WC1N 3JH | |
| 49 | Royal Manchester Childrens Hospital | Manchester | United Kingdom | M13 9WL | |
| 50 | Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle upon Tyne | United Kingdom | NE1 4LP | |
| 51 | Queens Medical Centre | Nottingham | United Kingdom | NG7 2UH | |
| 52 | Southampton General Hospital | Southampton | United Kingdom | SO16 6YD | |
| 53 | Royal Marsden Hospital; Pediatric Unit | Surrey | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01390948
Other Study ID Numbers:
- BO25041
- 2010-022189-28
- ITCC-019
- HGG-01
First Posted:
Jul 11, 2011
Last Update Posted:
Aug 6, 2020
Last Verified:
Jul 1, 2020
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Chemoradiation + temozolomide (TMZ) and Chemoradiation + Bevacizumab + TMZ arms: 174 participants were screened; 121 were randomized; 116 received study treatment. Young Patient Cohort: 4 participants were screened; 3 were enrolled and received study treatment (these subjects were not randomized and are not included in efficacy analyses). |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ | Bevacizumab + TMZ Young Patient Cohort (YPC) |
|---|---|---|---|
| Arm/Group Description | Participants received a total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks with 75 milligrams per meter squared (mg/m^2) TMZ daily for up to 49 days followed by a treatment break of approximately 4 weeks. The treatment break was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 milligrams per kilogram (mg/kg) every 2 weeks throughout the entire treatment period. | Participants aged >/= 6 months and < 3 years received 10 mg/kg Bevacizumab every 2 weeks and 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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. |
| Period Title: Overall Study | |||
| STARTED | 59 | 62 | 3 |
| Treated | 56 | 60 | 3 |
| COMPLETED | 44 | 44 | 2 |
| NOT COMPLETED | 15 | 18 | 1 |
Baseline Characteristics
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ | Bevacizumab + TMZ Young Patient Cohort (YPC) | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. | Participants aged >/= 6 months and < 3 years received 10 mg/kg Bevacizumab every 2 weeks and 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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. | Total of all reporting groups |
| Overall Participants | 59 | 62 | 3 | 124 |
| Age, Customized (Count of Participants) | ||||
| < 3 years |
0
0%
|
0
0%
|
3
100%
|
3
2.4%
|
| >/= 3 years and < 6 years |
6
10.2%
|
10
16.1%
|
0
0%
|
16
12.9%
|
| >/= 6 years and < 13 years |
30
50.8%
|
35
56.5%
|
0
0%
|
65
52.4%
|
| >/= 13 years and < 18 years |
23
39%
|
17
27.4%
|
0
0%
|
40
32.3%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
23
39%
|
28
45.2%
|
0
0%
|
51
41.1%
|
| Male |
36
61%
|
34
54.8%
|
3
100%
|
73
58.9%
|
Outcome Measures
| Title | Event-Free Survival (EFS) as Assessed by the Central Radiology Review Committee (CRRC) |
|---|---|
| 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 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. |
| Time Frame | From the time of randomization to the date of any defined event (up to 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Median (95% Confidence Interval) [months] |
11.79
|
8.21
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Chemoradiation + TMZ, Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1292 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.44 | |
| Confidence Interval |
(2-Sided) 95% 0.90 to 2.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Median (95% Confidence Interval) [months] |
20.27
|
18.30
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
67.69
114.7%
|
74.83
120.7%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
66.46
112.6%
|
68.43
110.4%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
48.37
82%
|
38.28
61.7%
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Median (95% Confidence Interval) [months] |
11.79
|
11.27
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | 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. |
| Time Frame | From the time of randomization to the date of any defined event (up to 12 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population with a measurable lesion at baseline. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 15 | 12 |
| Number (95% Confidence Interval) [percentage of participants] |
40
67.8%
|
41.7
67.3%
|
| Title | Concordance Between Structural Versus Multimodal Imaging for CRRC-Assessed Event-Free Survival |
|---|---|
| Description | 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. |
| Time Frame | Up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Number [percentage of participants] |
96.6
163.7%
|
87.1
140.5%
|
| Title | Health Status as Measured by the Health Utility Index (HUI) |
|---|---|
| Description | 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. |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population aged 5 years or older with a measure at the specified time point. Here, 'n' represents the number of participants with a measure at the specified time point. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 36 | 45 |
| Baseline |
0.713
(0.317)
|
0.730
(0.274)
|
| Cycle 6, Day 1 |
0.785
(0.239)
|
0.779
(0.232)
|
| End of Treatment |
0.832
(0.216)
|
0.820
(0.209)
|
| Yearly Follow-Up 1 |
0.906
(0.110)
|
0.926
(0.109)
|
| Yearly Follow-up 2 |
0.737
(0.326)
|
0.793
(0.219)
|
| Additional Safety Follow-Up (Visit 2) |
0.784
(0.287)
|
0.901
(0.147)
|
| Additional Safety Follow-Up (Visit 4) |
0.814
(0.304)
|
0.830
(0.143)
|
| Additional Safety Follow-Up (Visit 6) |
1.000
(0.000)
|
0.490
(0.537)
|
| Additional Safety Follow-Up (Visit 8) |
0.930
(NA)
|
|
| End of Study |
0.647
(0.496)
|
0.790
(0.234)
|
| Title | Neurological Psychological Function as Measured by the Wechsler Scale |
|---|---|
| Description | 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. |
| Time Frame | End of treatment (approximately 58 weeks post-baseline) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| Mean (Standard Deviation) [units on a scale] |
92.0
(9.8)
|
97.0
(18.4)
|
| Title | Percentage of Participants Who Completed >/= 90% of Planned Radiotherapy and TMZ Administrations |
|---|---|
| Description | |
| Time Frame | From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants that received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 56 | 60 |
| Radiotherapy |
94.6
160.3%
|
98.3
158.5%
|
| TMZ |
85.7
145.3%
|
88.3
142.4%
|
| Title | Percentage of Participants With a Treatment Delay or Discontinuation |
|---|---|
| Description | |
| Time Frame | From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participant population included all randomized participants regardless of whether they received study treatment. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 59 | 62 |
| AE leading to dose modification/interruption |
60.7
102.9%
|
71.7
115.6%
|
| AE leading to withdrawal from treatment |
5.4
9.2%
|
21.7
35%
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants that received study drug. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 56 | 60 |
| Median (Full Range) [Grays] |
54.0
|
54.0
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants that received study drug. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 56 | 60 |
| TMZ |
42.0
|
42.0
|
| Bevacizumab |
NA
|
6.0
|
| Title | Percentage of Participants With an Adverse Event (AE) |
|---|---|
| Description | 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. |
| Time Frame | From the time of randomization of the first participant to the date of clinical cutoff (approximately 60 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants that received study drug. |
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ |
|---|---|---|
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. |
| Measure Participants | 56 | 60 |
| Number [percentage of participants] |
100
169.5%
|
98.3
158.5%
|
Adverse Events
| Time Frame | From randomization/enrollment of the first participant to date of clinical cut off (approximately 60 months) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||
| Arm/Group Title | Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ | Bevacizumab + TMZ Young Patient Cohort (YPC) | |||
| Arm/Group Description | Participants received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 received 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 was followed by an adjuvant treatment phase where participants received 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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 was given concomitantly at a dose of 10 mg/kg every 2 weeks throughout the entire treatment period. | Participants aged >/= 6 months and < 3 years received 10 mg/kg Bevacizumab every 2 weeks and 150 to 200 mg/m^2 of TMZ daily on Days 1-5 of each cycle. TMZ was 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. | |||
All Cause Mortality |
||||||
| Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ | Bevacizumab + TMZ Young Patient Cohort (YPC) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ | Bevacizumab + TMZ Young Patient Cohort (YPC) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/56 (48.2%) | 35/60 (58.3%) | 0/3 (0%) | |||
| Blood and lymphatic system disorders | ||||||
| FEBRILE BONE MARROW APLASIA | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| FEBRILE NEUTROPENIA | 0/56 (0%) | 0 | 5/60 (8.3%) | 6 | 0/3 (0%) | 0 |
| THROMBOCYTOPENIA | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Endocrine disorders | ||||||
| PRECOCIOUS PUBERTY | 0/56 (0%) | 0 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Eye disorders | ||||||
| EYELID OEDEMA | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| CONSTIPATION | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| NAUSEA | 0/56 (0%) | 0 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| VOMITING | 3/56 (5.4%) | 3 | 6/60 (10%) | 8 | 0/3 (0%) | 0 |
| General disorders | ||||||
| CATHETER SITE THROMBOSIS | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| CYST | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| HYPOTHERMIA | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| IMPLANT SITE DEHISCENCE | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| INFLUENZA LIKE ILLNESS | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| PYREXIA | 5/56 (8.9%) | 6 | 12/60 (20%) | 17 | 0/3 (0%) | 0 |
| Immune system disorders | ||||||
| DRUG HYPERSENSITIVITY | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| HYPERSENSITIVITY | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| Infections and infestations | ||||||
| CATHETER SITE INFECTION | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| DEVICE RELATED INFECTION | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| DEVICE RELATED SEPSIS | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| GASTROENTERITIS | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| HERPES ZOSTER | 2/56 (3.6%) | 2 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| INFECTION | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| KLEBSIELLA BACTERAEMIA | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| PNEUMONIA | 1/56 (1.8%) | 1 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| PSEUDOMONAS INFECTION | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| SKIN INFECTION | 1/56 (1.8%) | 1 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| SOFT TISSUE INFECTION | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| SUBCUTANEOUS ABSCESS | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| TONSILLITIS | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| VASCULAR DEVICE INFECTION | 0/56 (0%) | 0 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| HAEMATURIA TRAUMATIC | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| RADIUS FRACTURE | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| Investigations | ||||||
| BODY TEMPERATURE INCREASED | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| LYMPHOCYTE COUNT DECREASED | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| NEUTROPHIL COUNT DECREASED | 1/56 (1.8%) | 1 | 1/60 (1.7%) | 2 | 0/3 (0%) | 0 |
| PLATELET COUNT DECREASED | 0/56 (0%) | 0 | 2/60 (3.3%) | 4 | 0/3 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| DECREASED APPETITE | 1/56 (1.8%) | 1 | 1/60 (1.7%) | 2 | 0/3 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| ATYPICAL TERATOID/RHABDOID TUMOUR OF CNS | 0/56 (0%) | 0 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| B-CELL TYPE ACUTE LEUKAEMIA | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| OSTEOSARCOMA | 0/56 (0%) | 0 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Nervous system disorders | ||||||
| CEREBRAL CYST | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| CEREBRAL ISCHAEMIA | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| CEREBROSPINAL FLUID LEAKAGE | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| DEPRESSED LEVEL OF CONSCIOUSNESS | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| HEADACHE | 2/56 (3.6%) | 2 | 4/60 (6.7%) | 5 | 0/3 (0%) | 0 |
| HEMIPARESIS | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| HYDROCEPHALUS | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| MONOPLEGIA | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| NERVOUS SYSTEM DISORDER | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| PARTIAL SEIZURES | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| PRESYNCOPE | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| SEIZURE | 7/56 (12.5%) | 12 | 5/60 (8.3%) | 5 | 0/3 (0%) | 0 |
| SOMNOLENCE | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| STATUS EPILEPTICUS | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| Product Issues | ||||||
| DEVICE OCCLUSION | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| Psychiatric disorders | ||||||
| CONFUSIONAL STATE | 0/56 (0%) | 0 | 2/60 (3.3%) | 3 | 0/3 (0%) | 0 |
| Renal and urinary disorders | ||||||
| PROTEINURIA | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| OROPHARYNGEAL PAIN | 1/56 (1.8%) | 2 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| BLISTER | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| RASH | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| URTICARIA | 1/56 (1.8%) | 1 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Vascular disorders | ||||||
| DEEP VEIN THROMBOSIS | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Chemoradiation + TMZ | Chemoradiation + Bevacizumab + TMZ | Bevacizumab + TMZ Young Patient Cohort (YPC) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 56/56 (100%) | 60/60 (100%) | 3/3 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| ANAEMIA | 6/56 (10.7%) | 13 | 5/60 (8.3%) | 9 | 0/3 (0%) | 0 |
| LEUKOPENIA | 6/56 (10.7%) | 11 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| LYMPHOPENIA | 3/56 (5.4%) | 4 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| NEUTROPENIA | 12/56 (21.4%) | 26 | 9/60 (15%) | 19 | 0/3 (0%) | 0 |
| THROMBOCYTOPENIA | 8/56 (14.3%) | 20 | 10/60 (16.7%) | 31 | 0/3 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| EAR PAIN | 2/56 (3.6%) | 2 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| Eye disorders | ||||||
| EYE PAIN | 4/56 (7.1%) | 4 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| ABDOMINAL PAIN | 10/56 (17.9%) | 17 | 12/60 (20%) | 18 | 1/3 (33.3%) | 1 |
| ABDOMINAL PAIN UPPER | 6/56 (10.7%) | 7 | 7/60 (11.7%) | 9 | 0/3 (0%) | 0 |
| CONSTIPATION | 12/56 (21.4%) | 19 | 18/60 (30%) | 29 | 0/3 (0%) | 0 |
| DENTAL CARIES | 0/56 (0%) | 0 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| DIARRHOEA | 13/56 (23.2%) | 19 | 14/60 (23.3%) | 22 | 2/3 (66.7%) | 2 |
| NAUSEA | 24/56 (42.9%) | 49 | 22/60 (36.7%) | 38 | 0/3 (0%) | 0 |
| ORAL PAIN | 0/56 (0%) | 0 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| TOOTHACHE | 3/56 (5.4%) | 3 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| VOMITING | 29/56 (51.8%) | 65 | 36/60 (60%) | 89 | 2/3 (66.7%) | 3 |
| General disorders | ||||||
| ASTHENIA | 4/56 (7.1%) | 7 | 6/60 (10%) | 6 | 0/3 (0%) | 0 |
| FATIGUE | 32/56 (57.1%) | 44 | 26/60 (43.3%) | 36 | 0/3 (0%) | 0 |
| INFLUENZA LIKE ILLNESS | 3/56 (5.4%) | 4 | 1/60 (1.7%) | 2 | 0/3 (0%) | 0 |
| PYREXIA | 16/56 (28.6%) | 27 | 15/60 (25%) | 31 | 1/3 (33.3%) | 2 |
| Infections and infestations | ||||||
| CANDIDA INFECTION | 2/56 (3.6%) | 4 | 0/60 (0%) | 0 | 1/3 (33.3%) | 1 |
| CONJUNCTIVITIS | 5/56 (8.9%) | 5 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| HERPES ZOSTER | 3/56 (5.4%) | 3 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| INFLUENZA | 1/56 (1.8%) | 1 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| NASOPHARYNGITIS | 6/56 (10.7%) | 6 | 10/60 (16.7%) | 10 | 0/3 (0%) | 0 |
| OTITIS MEDIA ACUTE | 0/56 (0%) | 0 | 0/60 (0%) | 0 | 1/3 (33.3%) | 1 |
| PHARYNGITIS | 4/56 (7.1%) | 4 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| RHINITIS | 9/56 (16.1%) | 10 | 8/60 (13.3%) | 9 | 0/3 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 7/56 (12.5%) | 7 | 3/60 (5%) | 6 | 2/3 (66.7%) | 4 |
| VIRAL INFECTION | 0/56 (0%) | 0 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| RADIATION INJURY | 3/56 (5.4%) | 3 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| RADIATION SKIN INJURY | 4/56 (7.1%) | 4 | 5/60 (8.3%) | 5 | 0/3 (0%) | 0 |
| Investigations | ||||||
| ALANINE AMINOTRANSFERASE INCREASED | 6/56 (10.7%) | 6 | 3/60 (5%) | 3 | 0/3 (0%) | 0 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 3/56 (5.4%) | 3 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| HEART RATE INCREASED | 0/56 (0%) | 0 | 1/60 (1.7%) | 1 | 1/3 (33.3%) | 1 |
| NEUTROPHIL COUNT DECREASED | 17/56 (30.4%) | 32 | 16/60 (26.7%) | 29 | 1/3 (33.3%) | 1 |
| NEUTROPHIL COUNT INCREASED | 3/56 (5.4%) | 3 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| PLATELET COUNT DECREASED | 19/56 (33.9%) | 46 | 18/60 (30%) | 42 | 1/3 (33.3%) | 2 |
| WEIGHT DECREASED | 3/56 (5.4%) | 3 | 6/60 (10%) | 8 | 0/3 (0%) | 0 |
| WHITE BLOOD CELL COUNT DECREASED | 14/56 (25%) | 28 | 16/60 (26.7%) | 32 | 1/3 (33.3%) | 1 |
| WHITE BLOOD CELL COUNT INCREASED | 4/56 (7.1%) | 5 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| DECREASED APPETITE | 21/56 (37.5%) | 28 | 17/60 (28.3%) | 22 | 0/3 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| ARTHRALGIA | 3/56 (5.4%) | 4 | 6/60 (10%) | 6 | 0/3 (0%) | 0 |
| BACK PAIN | 3/56 (5.4%) | 3 | 4/60 (6.7%) | 4 | 0/3 (0%) | 0 |
| MUSCULOSKELETAL PAIN | 5/56 (8.9%) | 5 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| NECK PAIN | 3/56 (5.4%) | 4 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| PAIN IN EXTREMITY | 4/56 (7.1%) | 5 | 3/60 (5%) | 3 | 1/3 (33.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| SKIN PAPILLOMA | 3/56 (5.4%) | 3 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Nervous system disorders | ||||||
| DIZZINESS | 2/56 (3.6%) | 2 | 3/60 (5%) | 5 | 0/3 (0%) | 0 |
| DYSGEUSIA | 4/56 (7.1%) | 4 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| HEADACHE | 32/56 (57.1%) | 66 | 34/60 (56.7%) | 63 | 0/3 (0%) | 0 |
| INTRACRANIAL PRESSURE INCREASED | 3/56 (5.4%) | 3 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| PARAESTHESIA | 4/56 (7.1%) | 5 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| SEIZURE | 5/56 (8.9%) | 10 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| SOMNOLENCE | 3/56 (5.4%) | 5 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| Psychiatric disorders | ||||||
| ANXIETY | 2/56 (3.6%) | 2 | 5/60 (8.3%) | 6 | 0/3 (0%) | 0 |
| INSOMNIA | 7/56 (12.5%) | 9 | 2/60 (3.3%) | 2 | 0/3 (0%) | 0 |
| Renal and urinary disorders | ||||||
| PROTEINURIA | 0/56 (0%) | 0 | 15/60 (25%) | 27 | 0/3 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| COUGH | 12/56 (21.4%) | 17 | 19/60 (31.7%) | 30 | 0/3 (0%) | 0 |
| EPISTAXIS | 4/56 (7.1%) | 4 | 12/60 (20%) | 19 | 0/3 (0%) | 0 |
| OROPHARYNGEAL PAIN | 5/56 (8.9%) | 11 | 7/60 (11.7%) | 8 | 0/3 (0%) | 0 |
| RHINORRHOEA | 2/56 (3.6%) | 2 | 7/60 (11.7%) | 7 | 0/3 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| ALOPECIA | 34/56 (60.7%) | 34 | 19/60 (31.7%) | 20 | 0/3 (0%) | 0 |
| DERMATITIS | 5/56 (8.9%) | 5 | 1/60 (1.7%) | 1 | 0/3 (0%) | 0 |
| DRY SKIN | 2/56 (3.6%) | 2 | 4/60 (6.7%) | 4 | 0/3 (0%) | 0 |
| ERYTHEMA | 2/56 (3.6%) | 2 | 7/60 (11.7%) | 9 | 0/3 (0%) | 0 |
| PRURITUS | 5/56 (8.9%) | 5 | 5/60 (8.3%) | 6 | 0/3 (0%) | 0 |
| PURPURA | 0/56 (0%) | 0 | 4/60 (6.7%) | 10 | 0/3 (0%) | 0 |
| RASH | 1/56 (1.8%) | 4 | 11/60 (18.3%) | 17 | 2/3 (66.7%) | 2 |
| SKIN STRIAE | 5/56 (8.9%) | 5 | 0/60 (0%) | 0 | 0/3 (0%) | 0 |
| URTICARIA | 5/56 (8.9%) | 8 | 8/60 (13.3%) | 10 | 0/3 (0%) | 0 |
| Vascular disorders | ||||||
| HYPERTENSION | 1/56 (1.8%) | 1 | 7/60 (11.7%) | 10 | 1/3 (33.3%) | 2 |
| HYPOTENSION | 2/56 (3.6%) | 2 | 4/60 (6.7%) | 4 | 0/3 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 1-800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01390948
Other Study ID Numbers:
- BO25041
- 2010-022189-28
- ITCC-019
- HGG-01
First Posted:
Jul 11, 2011
Last Update Posted:
Aug 6, 2020
Last Verified:
Jul 1, 2020