Phase III trial exploring the combination of bevacizumab and lomustine in patients with first recurrence of a glioblastoma
- Conditions
- glioblastoma10029211GBM
- Registration Number
- NL-OMON39944
- Lead Sponsor
- European Organisation for Research in Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 155
• Age >= 18 years
• WHO Performance status 0 - 2
• Availability of biological material (tumor) for central review processes and translational research
projects (tumor and blood)
• Histologically or biopsy proven glioblastoma multiforme
• Unequivocal first recurrence after prior treatment with radiotherapy with concurrent and/or adjuvant temozolomide
• Patient may have undergone surgery for the recurrence. If operated, residual and measurable disease after
surgery is not required but surgery must have confirmed the recurrence. Surgery should be completed for at least
4 weeks and patients should have fully recovered.
• For non operated patients, recurrent disease must be at least one bidimensionally measurable target lesion
(contrast enhancing lesion) with diameters of at least 1cm.
• Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.
• No prior treatment with bevacizumab or other VEGF signalling inhibitors
• No radiotherapy within the three months prior to the diagnosis of progression
• No chemotherapy in the past four weeks (or 6 weeks in case of nitrosourea*s)
• No non tumor related surgery or other invasive procedures (major surgical procedure, open biopsy or significant traumatic injury) within 4 weeks prior to randomization, or anticipation of the need for major surgery during the course of the study treatment.
• No core biopsy or other minor surgical procedure within 7 days prior to randomization. Placement of a central vascular access device (CVAD) if performed at least 2 days prior to study treatment administration is allowed
• No radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is
histologally proven
• Normal hematological functions: neutrophils >= 1.5 x 109 cells/l, platelets >=100 x 109 cells/l, Hb > 6.2 mmmol/l
• Normal liver function: bilirubin < 1.5 x upper limit of the normal range (ULN), alkaline phosphatase and
transaminases (ASAT/ALAT) < 2.5 x ULN, INR < 1,5
• Normal renal function: calculated or measured creatinine clearance < 30 mL/min; Urine dipstick for proteinuria <
2+. Patients with >=2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hours urine collection and
must demonstrate <=1 g of protein/24 hr. .
• Women of reproductive potential, female patients within one year of entering the menopause as well as males
must agree to use an effective non-hormonal method of contraception during the treatment period and for at least
6 months after the last dose of Bevacizumab.
• For premenopausal women: negative pregancy test, not lactating.
• No other diseases, interfering with follow up.
• No geographical, psychological or other non-medical conditions interfering with follow-up
• Written informed consent.
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• Arterial or venous thrombosis <= 6 nths prior to registration
• evidence of recent hemorrhage on 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
• History of myocardial infarction (<= 6 months prior to inclusion), unstable angina, New York Heart Association
(NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
• Uncontrolled hypertension defined by a systolic pressure > 150 mm Hg and/or diastolic pressure > 100 mm Hg,
with or without anti-hypertensive medication. Patients with initial blood pressure elevation are eligible if initiation or
adjustment of anti-hypertensive medication lowers pressure to meet the entry criteria.
• significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
• prior history of hypertensive crisis or hypertensive encephalopathy
• history of pulmonary haemorrhage/haemoptysis >= grade 2 according to the NCI-CTCAE
version 4.0 criteria within 1 month prior to randomization
• Current or recent (within 10 days of first dose of Bevacizumab) use of aspirin (> 325 mg/day) or other NSAID with anti-platelet activity or treatment with dipyramidole, ticlopidine, clopidogrel and cilostaz.
• International normalized ratio (INR) > 1.5 ULN and activated partial thromboplastin time (aPTT) > 1.5 × the ULN. 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 atient has been on a stable dose of anticoagulants for at least two weeks before randomization. s per ASCO guidelines, LMWH should be the preferred approach.
• Clinically serious (as judged by the investigator) non-healing wounds, active skin ulcers or incompletely healed
bone fracture.
• History of active gastroduodenal ulcer(s).
• History of abdominal fistula as well as non-GI fistula, gastrointestinal perforation or intra-abdominal abscess
within 6 months prior to inclusion.
• History of intracranial abscess within 6 months prior to randomization
• Patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be switched to non-EIAED at least 2 weeks prior to randomization
• Evidence of any active infection requiring hospitalization or antibiotics, within 2 weeks prior to day 1 of cycle 1.
• Current or recent (within 4 weeks of enrollment) treatment with another investigational drug.
• Known hypersensitivity to any excipients of Bevacizumab formulation.
• Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibody.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall survival </p><br>
- Secondary Outcome Measures
Name Time Method <p>Median progression free survival (PFS), PFS6, PFS12, median OS, OS 9, OS 12,<br /><br>OS24, best overall response distribution, objective and complete response rates<br /><br>and median duration of objective or complete response; quality of life and<br /><br>neurocognitive function, steorid use; pattern of relapse</p><br>