Phase 2
N=124
A Study of Bevacizumab (Avastin) in Combination With Temozolomide (TMZ) and Radiotherapy in Paediatric and Adolescent Participants With High-Grade Glioma
High Grade Glioma
Bottom Line
View on ClinicalTrials.gov: NCT01390948 ↗Enrolled (actual)
124
Serious AEs
52.1%
Results posted
Aug 2017
Primary outcome: Primary: Event-Free Survival (EFS) as Assessed by the Central Radiology Review Committee (CRRC) — 11.79; 8.21 months — p=0.1292
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bevacizumab (Drug); Radiotherapy (Radiation); Temozolomide (TMZ) (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Feb 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Event-Free Survival (EFS) as Assessed by the Central Radiology Review Committee (CRRC) |
11.79; 8.21 | 0.1292 |
| SECONDARY Overall Survival |
20.27; 18.30 | — |
| SECONDARY Percentage of Participants With 1-Year Survival |
67.69; 74.83 | — |
| SECONDARY Percentage of Participants With EFS as Determined by the CRRC at 6 Months |
66.46; 68.43 | — |
| SECONDARY Percentage of Participants With EFS as Determined by the CRRC at 1 Year |
48.37; 38.28 | — |
| SECONDARY EFS as Assessed by the Investigator |
11.79; 11.27 | — |
| SECONDARY Objective Response Rate (ORR) |
40; 41.7 | — |
| SECONDARY Concordance Between Structural Versus Multimodal Imaging for CRRC-Assessed Event-Free Survival |
96.6; 87.1 | — |
| SECONDARY Health Status as Measured by the Health Utility Index (HUI) |
0.713; 0.730; 0.785; 0.779; 0.832; 0.820 | — |
| SECONDARY Neurological Psychological Function as Measured by the Wechsler Scale |
92.0; 97.0 | — |
| SECONDARY Percentage of Participants Who Completed >/= 90% of Planned Radiotherapy and TMZ Administrations |
94.6; 98.3; 85.7; 88.3 | — |
| SECONDARY Percentage of Participants With a Treatment Delay or Discontinuation |
60.7; 71.7; 5.4; 21.7 | — |
| SECONDARY Number of Radiotherapy Dose Administrations in the Concurrent Phase |
54.0; 54.0 | — |
| SECONDARY Number of Dose Administrations of TMZ and Bevacizumab in the Concurrent Phase |
42.0; 42.0; NA; 6.0 | — |
| SECONDARY Percentage of Participants With an Adverse Event (AE) |
100; 98.3 | — |
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.
Eligibility Criteria
Inclusion Criteria - Main cohort :
- Paediatric participants, aged >= 3 years and = 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
Data sourced from ClinicalTrials.gov (NCT01390948). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.