Phase III trial of CCNU/temozolomide (TMZ) combination therapy vs. standard TMZ therapy for newly diagnosed MGMT-methylated glioblastoma patients (CeTeG)
- Conditions
- ewly diagnosed patients with glioblastoma harbouring a methylated MGMT promoterMedDRA version: 18.1Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2009-011252-22-DE
- Lead Sponsor
- Medical Faculty, University of Bonn
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
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, histology confirmed by reference neuropathology (Insitute of Neuropathology, University of Bonn Medical Center, Prof. Dr. Pietsch). Histology obtained by complete resection, partial resection, open biopsy or stereotactic biopsy
Methylated MGMT promoter in the tumor as determined by Oncomethylome (Amsterdam) using methylation-specific PCR
Males or females 18-70 years of age, 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 (intrauterine device, birth control pills, or barrier device) during and for 3 months after the trial (Pearl index <1%)
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:oAdequate 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),
alanine transaminase (ALT/SGPT) and aspartate transaminase (AST/SGOT) < 3 times ULN
Adequate renal function: creatinine < 1.5 times ULN
Adequate blood clotting:
PT and PTT within normal limits
Negative HIV test
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
Prior malignancy (unless adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer), unless the prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsquent evidence of recurrence
Prior chemotherapy, systemic or local treatment with DNA-damaging agents, tyrosine kinase inhibitors or anti-angiogenic agents for any cancer
prior RT to the brain
Concurrent administration of any other anti-tumor therapy not described in the protocol
Allergy or other intolerability of temozolomide or CCNU
Unable to undergo MRI
Past medical history of diseases with poor prognosis, e.g. severe coronary heart disease, heart failure (NYHA III/IV), severe and poorly controlled diabetes, immune deficiency, residual deficits after stroke, severe mental retardation or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
Known HIV infection, active Hepatitis B or C infection
Any active infection (at the discretion of the investigator)
Female patients that are pregnant or breastfeeding
Patients with reproductive potential who do not accept to use contraception during the trial and 3 months thereafter
Treatment in another clinical trial with therapeutic intervention or use of any other investigational agent within the 30 days before enrolment
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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: This phase III trial determines whether combined Cecenu and Temozolomide chemotherapy plus standard radiotherapy is superior to TMZ monochemotherapy plus standard radiotherapy alone in patients with newly diagnosed mMGMT GBM patients regarding overall survival.<br><br>;Secondary Objective: Secondary objectives are to determine whether combined CCNU/TMZ/RT therapy is superior to standard TMZ/RT therapy regarding progression-free survival and time to treatment failure as well as to determine acute and late toxicity of CCNU/TMZ therapy including its effects such as the delay of subsequent courses due to acute toxicity.;Primary end point(s): Overall survival (OS) as measured from the day of randomization until death<br><br>
- Secondary Outcome Measures
Name Time Method