A Phase II Open Label Randomised Multicentric Study in Patients With Unresectable Glioblastoma Using Neo-adjuvant Treatment With Two Cycles of Temozolomide Previous Temozolomide Plus Radiation Therapy and Adjuvant Temozolomide vs. Neo-adjuvant Treatment With Two Cycles of Temozolomide Plus Bevacizumab Previous Temozolomide, Bevacizumab and Radiation Therapy and Adjuvant Temozolomide.
1. Patients with glioblastoma, non-resectable, biopsy only. Accepting a craniotomy with
resection attempted if an RMN within a period of about 72 hours to confirm that the
resection was less than 25% of the tumor and fulfill criterion
2. Measurable disease and contrast uptake ≥ 3 cm in one of its diameters.
3. Stable doses of dexamethasone during the week prior to inclusion.
4. Performance Status ≤ 2.
5. Age ≤ 75 years.
6. MiniMental Status> 25/30.
7. Bartel index > 50%.
8. The surgical incision should be healed prior to randomization. The treatment can be
started at 3 weeks of a simple stereotactic biopsy or 4 weeks in case of open biopsy
9. Maximum baseline MRI performed 4 weeks before starting treatment (acceptance of the
MRI done for neuronavegation biopsy as baseline).
10. Adequate bone marrow reserve: neutrophils>2000x109/L, platelets>100x109/L,
11. Not received prior treatment with chemotherapy or radiation.
12. Adequate renal function: Creatinine <1.5 ULN of the laboratory performing the
13. Adequate liver function: Serum bilirubin <1.5/ULN SGOT, SGPT<2.5ULN. Serum alkaline
14. Absence of proteinuria.
15. Effective method of contraception for patients and their partners.
16. Written informed consent
17. Collecting material for a double histological confirmation of diagnosis.
1. Prior radiotherapy or chemotherapy for the treatment of glioma.
2. Less than 5 years prior to any invasive neoplasia. Accepted carcinoma in situ of
cervix carcinoma or cutaneous vasocelular.
3. Cerebral hemorrhage after biopsy.
4. Pregnancy or lactation.
5. Clinically significant cardiovascular disease: - Myocardial infarction or unstable
angina (≤ 6 months before randomization) - Congestive heart failure (CHF) class ≥ II
NYHA, New York Heart Association. - Cardiac Arrhythmia uncontrolled despite
medication (may include patients with atrial fibrillation often controlled). -
Peripheral vascular disease ≥ grade 3 (ie, symptomatic and interfering with everyday
activities or specifying repairs or review).
6. Continued use of aspirin> 325 mg / day, currently or recently (within the 10 days
prior to randomization).
7. Currently established treatment with therapeutic doses of anticoagulants Coumarin
derivatives (courmarina, warfarin) or a week before starting treatment. It allows the
administration of heparin for control of Deep Vein Thrombosis (DVT)
8. Patients with PTSD and patients with inflammatory bowel disease, with risk of
9. HT with values above 150 mmHg systolic pressure of 100 mmHg and diastolic tension is
not controllable with standard antihypertensive drugs.
10. Not healed scars, ulcers or recent bone fracture.
11. Bleeding diathesis or coagulopathy.