Overview

This trial is active, not recruiting.

Condition high grade glioma
Treatments bevacizumab, radiotherapy, temozolomide (tmz)
Phase phase 2
Sponsor Hoffmann-La Roche
Start date October 2011
End date March 2020
Trial size 123 participants
Trial identifier NCT01390948, 2010-022189-28, BO25041, HGG-01, ITCC-019

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants will receive treatment with TMZ and bevacizumab.
bevacizumab Avastin
Participants will receive 10 milligrams per kilogram every 2 weeks during the study for 12 cycles, each cycle length of 28 days.
temozolomide (tmz)
Participants will receive 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/days 1-5 from the 2nd cycle onwards depending on the tolerance during the 1st cycle. Cycle length = 28 days.
(Experimental)
Participants will receive chemoradiation along with TMZ and bevacizumab during the chemoradiation phase, treatment with only bevacizumab during the treatment break phase and treatment with TMZ and bevacizumab during the TMZ adjuvant treatment phase.
bevacizumab Avastin
Participants will receive 10 milligrams per kilogram every 2 weeks during the study for 12 cycles, each cycle length of 28 days.
radiotherapy
Participants will receive a total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.
temozolomide (tmz)
Participants will receive 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/days 1-5 from the 2nd cycle onwards depending on the tolerance during the 1st cycle. Cycle length = 28 days.
(Active Comparator)
Participants will receive chemoradiation along with TMZ during the chemoradiation phase, no treatment during the treatment break phase and treatment with TMZ during the TMZ adjuvant treatment phase.
radiotherapy
Participants will receive a total dose of 54 Grey (Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation phase.
temozolomide (tmz)
Participants will receive 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/days 1-5 from the 2nd cycle onwards depending on the tolerance during the 1st cycle. Cycle length = 28 days.

Primary Outcomes

Measure
Event-Free Survival Defined as the Earliest Occurrence of Any One of the Following: Tumor progression, Tumor recurrence, Second Primary non- HGG Malignancy or Death Attributable to Any Cause as Determined by the Central Radiology Review Committee (CRRC)
time frame: Approximately 5 years

Secondary Outcomes

Measure
Overall Survival
time frame: Approximately 8 years
1-Year Overall Survival
time frame: 1 year
6-Months EFS Defined as the Earliest Occurrence of Any One of the Following: Tumor Progression, Tumor Recurrence, Second Primary Non-HGG Malignancy or Death Attributable to Any Cause as Determined by the CRRC
time frame: 6 months
1-year EFS Defined as the Earliest Occurrence of Any One of the Following: Tumor Progression, Tumor Recurrence, Second Primary Non-HGG Malignancy or Death Attributable to Any Cause as Determined by the CRRC
time frame: 1 year
EFS Defined as the Earliest Occurrence of Any One of the Following: Tumor Progression, Tumor Recurrence, Second Primary Non-HGG Malignancy or Death Attributable to Any Cause Determined by the Investigator
time frame: Approximately 5 years
Neurological Psychological Function as Measured by the Wechsler Scale Between the Treatment Arms
time frame: Approximately 5 years
Percentage of Participants with Adverse Events
time frame: Approximately 5 years
Percentage of Participants with Overall Response as Determined by the CRRC based on Response Assessment in Neuro-Oncology (RANO) Criteria
time frame: Approximately 5 years
Functional Changes in Tumor Assessed by MRI
time frame: Approximately 5 years
Health Status as Measured by the Health Utility Index (HUI) Between the Treatment Arms (for Participants Aged 5 Years and Older)
time frame: Approximately 5 years

Eligibility Criteria

Male or female participants from 6 months up to 18 years old.

Inclusion Criteria: - 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: - 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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.