Phase III Trial of CCNU/Temozolomide (TMZ) Combination Therapy vs. Standard TMZ Therapy for Newly Diagnosed MGMT-methylated Glioblastoma Patients
Inclusion Criteria:
- written informed consent
- patients have to be in a cognitive state that allows them to understand the rationale
and necessity of study therapy and procedures.
- newly diagnosed histologically proven GBM or gliosarcoma WHO Grad IV
- methylated MGMT promoter in the tumor
- estimated life expectancy of at least 12 weeks
- Karnofsky Performance Score (KPS) ≥ 70%
- patient compliance and geographic proximity that allow adequate follow up
- male and female patients with reproductive potential must use an approved
contraceptive method
- pre-menopausal female patients with childbearing potential: a negative serum
pregnancy test must be obtained prior to treatment start
- Adequate organ function as described below:
Adequate bone marrow reserve:
white blood cell (WBC) count > 3000/µl, granulocyte count >1500/µl, platelets >
100000/µl, haemoglobin ≥ 10 g/dl Adequate liver function bilirubin < 1.5 times above upper
limit of normal range (ULN), ALT and AST < 3 times ULN creatinine < 1.5 times ULN
Adequate blood clotting:
PT and PTT within normal limits Negative HIV test
Exclusion Criteria:
- prior malignancy
- prior chemotherapy
- prior radiotherapy to the brain
- concurrent administration of any other anti-tumor therapy
- allergy or other intolerability of temozolomide, CCNU, dacarbazine or other
nitrosourea derivatives
- unable to undergo MRI
- past medical history of diseases with poor prognosis
- known HIV infection, active Hepatitis B or C infection
- any active infection
- female patients that are pregnant or breastfeeding
- patients with reproductive potential who do not accept to use contraception
- treatment in another clinical trial
- any psychological, cognitive, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up scheduled
visits (at the discretion of investigator)