Newly Diagnosed Non Methylated Glioblastoma Multiforme Grade 4
Conditions
Keywords
Glioblastoma Multiforme
Brief summary
Cilengitide 2000 mg flat i.v. twice weekly is administered over a period of 18 months without interruption. Starting one week after the initiation of Cilengitide, RTX (60 Gy, 2 Gy per fraction) with concurrent daily temozolomide (60 mg/m2 p.o.) and daily procarbazine (PCB, 50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) is given over a period of 6 weeks (RTX Monday to Friday, both TMZ and PCB seven days a week). After a break of 4 weeks, adjuvant TMZ (50mg/m2 p.o in first cycle, 60 mg/m2 p.o. in subsequent cycles) and PCB (50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) are then given daily D1 to 20. This TMZ/PCB cycle is repeated every 28 days over a total period of 6 cycles.
Interventions
DRUGCilengitide
Cilengitide 2000 mg flat i.v. twice weekly is administered over a period of 18 months without interruption. Starting one week after the initiation of Cilengitide, RTX (60 Gy, 2 Gy per fraction) with concurrent daily temozolomide (60 mg/m2 p.o.) and daily procarbazine (PCB, 50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) is given over a period of 6 weeks (RTX Monday to Friday, both TMZ and PCB seven days a week). After a break of 4 weeks, adjuvant TMZ (50mg/m2 p.o in first cycle, 60 mg/m2 p.o. in subsequent cycles) and PCB (50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) are then given daily D1 to 20. This TMZ/PCB cycle is repeated every 28 days over a total period of 6 cycles.
Sponsors
Merck KGaA, Darmstadt, Germany
Northern Sydney and Central Coast Area Health Service
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed supratentorial GBM (WHO Grade IV,including GBM subtypes, e.g. gliosarcoma), histopathologically confirmed by central assessment as part of the screening for the CENTRIC trial. 2. Males or females ≥18 years of age. 3. Proven unmethylated MGMT gene promoter status, centrally assessed as part of the screening for the CENTRIC trial. 4. Written informed consent for the present trial obtained before undergoing any study-related activities. The informed consent also allows access to all information obtained during the screening for the CENTRIC trial, notably the result of the MGMT testing. 5. Available post-operative Gd-MRI performed within \<48 hours after surgery (in case it was not possible to obtain a Gd-MRI within \<48 hours post surgery, a Gd-MRI is to be performed prior to randomization). 6. Stable or decreasing dose of steroids for \>5 days prior to randomization. 7. ECOG PS of 0-1. 8. Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment. 9. Meets one of the following RPA classifications: * Class III (age \<50 years and ECOG PS 0). * Class IV (meeting one of the following criteria: 1. Age \<50 years and ECOG PS 1 or 2. Age ≥50 years, underwent prior partial or total tumor resection, Mini Mental State Examination \[MMSE\]≥27). * Class V (meeting one of the following criteria: 1. Age ≥50 years and underwent prior partial or total tumour resection, MMSE \<27 or 2. Age ≥50 years and underwent prior tumor biopsy only). 10. Laboratory values (within 2 week prior to randomization): * Absolute neutrophil count ≥1500/mm3. * Platelets ≥ 100,000/mm3. * Creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance rate ≥60 mL/min * Prothrombin time (PT) international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits. * Hemoglobin ≥10 g/dL. * Total bilirubin ≤1.5 x the ULN. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN(except when attributable to anticonvulsants). * Alkaline phosphatase ≤ 2.5 x ULN.
Exclusion criteria
Subjects are not eligible for this study, if they fulfill one or more of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 12 month progression free survival | 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response | 3 years | MRI review |
| Toxicity | 3 years | Utilising NCI CTC v 3.0 |
| Peripheral WBC MGMT modulation | 3 years | Blood collection and analysis |
| biomarker correlation with response | 3 years | using multiplex bioassay analysis |
Countries
Australia
Outcome results
None listed