Glioblastoma MedDRA version: 14.1 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent 2. Age greater than or equal to 18 years 3. Present with newly diagnosed supratentorial Glioblastoma (GBM) with a tissue diagnosis that has been established following either a surgical resection or biopsy. This includes treatment-naïve -(chemotherapy and radiotherapy)- patients with prior diagnosis of a lower grade astrocytoma that has been upgraded to a histologically verified GBM 4. Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomisation. Study treatment should be initiated = 28 days and = 49 days following the last surgical procedure (including biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) 5. WHO performance status = 2 6. Patient must have at least 1 formalin fixed paraffin embedded tumour tissue block representative of glioblastoma available for pathology central review and analysis of MGMT status. If tumour block is not available or not of adequate quality, sufficient pathology material, representative of glioblastoma, must be available for central review. 7. Stable or decreasing corticosteroids dose within 5 days prior to randomization 8. Adequate hematological function: • Absolute neutrophil count (ANC) = 1.5 x 1'000'000'000/L • Platelet count = 100 x 1'000'000'000/L • Haemoglobin = 10 g/dL (may be transfused to maintain or exceed this level) 9. Adequate liver function • Total bilirubin = 1.5 x ULN • AST and ALT = 2.5 x ULN 10. Adequate renal function •Creatinine = 1.25 x ULN • Urine dipstick for proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range 258
Exclusion criteria
Exclusion criteria: Disease and Treatment History 1. Evidence of recent hemorrhage on postoperative MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor are permitted entry into the study 2. Previous centralized screening for MGMT status for enrolment into a clinical trial 3. Any prior chemotherapy (including carmustine-containing wafers (Gliadel®) or immunotherapy (including vaccine therapy) for glioblastomas and low grade astrocytomas NOTE: 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent 4. Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field Bevacizumab related Exclusion Criteria 5. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 m Hg) 6. Prior history of hypertensive crisis or hypertensive encephalopathy 7. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix 6) 8. History of myocardial infarction or unstable angina within 6 months prior to randomization 9. History of stroke or TIAs within 6 months prior to randomization 10.Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization 11.History of = grade 2 haemoptysis according to the NCI-CTC criteria within 1 month prior to randomization 12.Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation) 13.Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury within 28 days prior to randomization 14.Core biopsy (excluding intracranial biopsy) or other minor surgical procedure within 7 days prior to randomization. Placement of a central vascular access device (CVAD) if performed within 2 days prior to bevacizumab/placebo administration 15.History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization 16.History of intracranial abscess within 6 months prior to randomization 17.Serious non-healing wound, active ulcer or untreated bone fracture 18.Pregnant or lactating females. NOTE: Serum pregnancy test to be assessed within 7 days prior to study treatment start 19.Fertile women < 2 years after last menstruation and men (surgically sterilized and of childbearing potential) unwilling or unable to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) General Exclusion Criteria 20.Any other malignancy within 5 years prior to randomization, except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix 21.Evidence of any active infection requiring hospitalization or IV antibiotics within 2 weeks prior to randomization 22.Patients who have any other disease, either metabolic or psychological, or who have any evidence on clinical examination or special investigations (including a laboratory finding) which gives reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug, or that may affect the patient’s co
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate the superiority in overall survival (OS) when bevacizumab is added to temozolomide with radiotherapy followed by temozolomide for the treatment of patients with newly diagnosed glioblastoma • To demonstrate the superiority in progression-free survival (PFS) as assessed by the investigator (using adapted MacDonald criteria) when bevacizumab is added to temozolomide with radiotherapy followed by temozolomide for the treatment of patients with newly diagnosed glioblastoma;Secondary Objective: • To compare PFS as assessed by an IRF between treatment arms • To compare 1-year and 2-year survival rates between treatment arms • To evaluate and compare the safety profile between treatment arms • To compare health-related quality of life (EORTC QLQ-C30, BN20) between treatment arms ;Primary end point(s): • OS, defined as the time between randomization and death due to any cause. Patients without an event will be censored the last time they were known to be alive. • PFS, as assessed by the investigator. PFS is defined as the time between randomization and disease progression (using adapted MacDonald Response Criteria) or death due to any cause. Patients without an event will be censored at the date of last follow up for progression. Patients with no post baseline follow up for progression will be censored at the day of randomization. For submission purposes in the United States, patients who receive non protocol specified anti-cancer therapy (NPT) will be censored at the last tumour assessment prior to receiving NPT. Also, only deaths occurring within 112 days (two tumour assessments) of the last tumour assessment will be counted as events ;Timepoint(s) of evaluation of this end point: - Final OS analysis: when 683 of deaths events are registered (to achieve 80% power of the log rank test at a 2-sided overall 4% alpha level) - Final PFS: occurred on beginning of August 2012 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) PFS, as assessed by an IRF. 2) 1-year and 2-year survival rates. 3) Safety profile. 4) Health-related quality of life;Timepoint(s) of evaluation of this end point: 1) occurred on beginning of August 2012 2) interim results on August 2012, final when 683 events are registered 3) interim results on August 2012, final when 683 events are registered 4) occurred on beginning of August 2012 | — |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed