Bevacizumab in Recurrent Grade II and III Glioma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01164189
• Date of registration: 15/07/2010
• Prospective Registration: Yes
• Primary sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Public title: Bevacizumab in Recurrent Grade II and III Glioma TAVAREC
• Scientific title: Randomized Trial Assessing the Significance of Bevacizumab in Recurrent Grade II and Grade III Gliomas - The TAVAREC Trial
• Date of first enrolment: February 2011
• Target sample size: 155
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01164189
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Austria, Belgium, France, Germany, Israel, Italy, Netherlands, Switzerland, United Kingdom

Contacts

• Name: Ahmed Idbaih
• Affiliation: CHU Pitie-Salpetriere

• Name: Martin J. van Den Bent, MD
• Affiliation: Daniel Den Hoed Cancer Center at Erasmus Medical Center

Key inclusion & exclusion criteria

- Histologically proven grade II or grade III astrocytoma, oligodendroglioma or
oligoastrocytoma according to the WHO 2007 at initial diagnosis.

- Demonstrated absence of 1p/19q co-deletion according to local diagnosis.

- Availability of biological material for central review processes and translational
research projects

- First recurrence after initial treatment with either radiotherapy and/or chemotherapy.

- Enhancing recurrence on MRI scan.

- For non operated patients, recurrent disease must be at least one bi-dimensionally
measurable contrast-enhancing lesion with clearly defined margins by MRI scan, with
minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on MRI
scan done within two weeks prior to start of randomisation.

- Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.

- No more than one line of chemotherapy (concurrent and adjuvant temozolomide
chemotherapy is considered one line of chemotherapy)

- If given, chemotherapy must have consisted of either temozolomide or PCV, and
patients must be off chemotherapy treatment for more than 6 months without
progression.

- No radiotherapy within the three months prior to the diagnosis of progression

- No radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy
unless the recurrence is histologically proven

- No current or recent (within 4 weeks before randomization) treatment with another
investigational drug

- No prior treatment with Bevacizumab or other VEGF inhibitors or VEGF-Receptor
signaling inhibitors

- No invasive procedures (surgical resection, open biopsy, significant traumatic injury
or any other major surgery involving entry into a body cavity) within 4 weeks prior to
randomization, or anticipation of the need for major surgery during the course of the
study treatment.

- No 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 at least 2 days prior to bevacizumab administration is allowed.

- Patient may have undergone surgery for recurrence. If operated, residual and
measurable disease after surgery is not required but histology must have confirmed the
recurrence. 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.

- No previous other malignancies, except for any previous malignancy which was treated
with curative intent more than 5 years prior to randomisation, and except for
adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of
the skin or carcinoma in situ of the cervix

- Absence of any cardiovascular disorder, including but not limited to:

- No history of myocardial infarction, unstable angina within 6 months prior to
randomisation

- No "New York Heart Association" (NYHA) Grade II or greater congestive heart
failure, or serious cardiac arrhythmia requiring medication.

- No significant vascular disease (e.g. aortic aneurysm requiring surgical repair
or recent peripheral arterial thrombosis) within 6 months prior to randomisation

- No prior history of hypertensive crisis or hypertensive encephalopathy

- No inadequately controlled hypertension (defined as systolic blood pressure >150
mmHg and/or diastolic blood pressure >100 m Hg)

- Absence of any thrombotic or hemorrhagic event, including but not limited to:

- No 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

- No history or evidence of inherited bleeding diathesis or coagulopathy with the
risk of bleeding.

- No arterial or venous thrombosis = 12 months prior to randomization

- No history of stroke or TIAs within 6 months prior to randomization

- No history of pulmonary haemorrhage/haemoptysis = grade 2 according to the
NCI-CTCAE version 4.0 criteria within 1 month prior to randomization

- Absence of 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 or cilostaz.

- International normalized ratio (INR) > 1.5 ULN and activated partial
thromboplastin time (aPTT) > 1.5 × the ULN. Patients using full-dose
anticoagulants at baseline are excluded from the study; but prevention of
thrombosis with low-dose anticoagulant is allowed

- Absence of known hypersensitivity

- to any part of the Bevacizumab or Temozolomide formulations.

- to Chinese hamster ovary cell products or other recombinant human or humanized
antibody.

- No underlying or previous conditions that could interfere with treatment, including
but not limited to:

- No history of intracranial abscess within 6 months prior to randomisation

- No clinically serious (as judged by the investigator) non-healing wounds, active
skin ulcers or incompletely healed bone fracture.

- No history of active gastroduodenal ulcer(s).

- No history of abdominal fistula as well as non-GI fistula, gastrointestinal
perforation or intraabdominal abscess within 6 months prior to inclusion.

- No evidence of active infection requiring hospitalization or antibiotics, within
2 weeks prior to randomisation.

- No other diseases, interfering with follow up.

- Normal hematological functions: neutrophils = 1.5 x 109 cells/l, platelets =100 x 109
cells/l and Hb = 6.2 mmol/l (9.9 g/dl).

- Normal liver function: bilirubin < 1.5 x upper limit of the normal range (ULN),
alkaline phosphatase and transaminases (ASAT) < 2.5 x ULN, INR < 1.5 ULN.

- Normal renal function: calculated (Cockcroft-Gault) 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.

- Age = 18 years




Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Central Nervous System Tumors

Intervention(s)

Drug: Temozolomide

Biological: Bevacizumab

Primary Outcome(s)

Probability of survival at 1 year [Time Frame: From the date of randomization up to the date of death, assessed up to 12 months]

Secondary Outcome(s)

Quality of life of patients and caregivers/relatives [Time Frame: At baseline and every 3 months untill lost to follow-up]

Clinical/neurological deterioration-free survival [Time Frame: From the date of randomization until the date of neurological deterioration]

Safety [Time Frame: After the first ten patients in each arm have completed the first two cycles or have stopped treatment, an interim safety review of those patients will be conducted.]

Objective response rate and duration of response [Time Frame: From the date of randomization until disease progression]

Progression-free survival [Time Frame: From the date of randomization until the date of objective progression or the date of patient's death whichever occurs first]

Cognitive deterioration [Time Frame: At baseline and every 3 months untill lost to follow-up]

Overall survival and survival at 24 months [Time Frame: From the date of randomization up to the date of death]

Steroid use [Time Frame: At baseline and every 3 months untill lost to follow-up]

Secondary ID(s)

2009-017422-39

EORTC-26091

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Hoffmann-La Roche