A randomized, double blind, placebo controlled, multicenter Phase III trial of bevacizumab, temozolomide and radiotherapy, followed by bevacizumab and temozolomide versus placebo, temozolomide and radiotherapy followed by placebo and temozolomide in patients with newly diagnosed glioblastoma

Phase 1

• Conditions: Glioblastoma; MedDRA version: 9.1Level: LLTClassification code 10018336Term: Glioblastoma

• Registration Number: EUCTR2008-006146-26-FR
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-24
• Last Update Posted: 4 July 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 920

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 < 2+. Patients discovered to have = 2+ proteinuria
on dipstick urinalysis at baseline should undergo a 24 hour urine collection and
must demonstrate = 1.0 g of protein in 24 hours
OR
• Urine protein/creatinine ratio (UPC) = 1.0
11. International normalized ratio (INR) or PT (secs) and activated partial
thromboplastin time (aPTT):
• 1.5 x ULN (except for subjects receiving anticoagulation therapy) in the absence
of therapeutic intent to anticoagulate the subject
• within therapeutic limits (according to the medical standard in the institution) in
the presence of therapeutic intent to anticoagulate the subject
NOTE: Use of full-dose anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks before randomization. As per ASCO guidelines, LMWH should be the preferred approach
12. Willing and able to comply with the protocol as judged by the investigator

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 previous malignancy which was treated with curative intent 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 (in

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified