Temozolomide and Procarbazine With Cilengitide for Patients With Glioblastoma Multiforme Without Methylation of the MGMT Promoter Gene

Launched by NORTHERN SYDNEY AND CENTRAL COAST AREA HEALTH SERVICE · May 14, 2010

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Eligibility criteria

• 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 exclusion criteria:
• • 1. Prior chemotherapy within the last 5 years.
• • 2. Prior RTX of the head.
• • 3. Receiving concurrent investigational agents or has received an investigational agent(s) within the past 30 days prior to the first dose of Cilengitide .
• • 4. Prior systemic antiangiogenic therapy.
• • 5. Placement of Gliadel® wafer at surgery.
• • 6. Treatment with a prohibited concomitant medication.
• • 7. Planned surgery for other diseases (e.g. dental extraction).
• • 8. History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
• • 9. History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥ 5 years are eligible for this study.
• • 10. History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• • 11. Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial infarction during the past 6 months. Uncontrolled arterial hypertension.
• • 12. Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
• • 13. Subject is pregnant (positive serum beta human chorionic gonadotropin \[β-HCG\] test at screening) or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
• • 14. Current alcohol dependence or drug abuse.
• • 15. Known hypersensitivity to the study treatment.
• • 16. Legal incapacity or limited legal capacity.
• • 17. Inability to undergo Gd-MRI.
• • 18. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• • 19. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or of family members who suffer(ed) from such.