Cilengitide in subjects with newly diagnosed glioblastoma multiforme and unmethylated MGMT gene promoter - a multicenter, open-label Phase II study, investigating two cilengitide regimens in combination with standard treatment (temozolomide with concomitant radiation therapy, followed by temozolomide maintenance therapy) - CORE. - CORE
- Conditions
- ewly diagnosed glioblastoma multiforme with unmethylated MGMT gene promoter statusMedDRA version: 9.1Level: LLTClassification code 10018337Term: Glioblastoma multiforme
- Registration Number
- EUCTR2008-004457-15-FR
- Lead Sponsor
- Merck KGaA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 265
1. Written informed consent obtained before undergoing any study-related activities.
2. Newly diagnosed histologically proven supratentorial GBM (World Health Organization [WHO] Grade IV, including GBM subtypes, e.g. gliosarcoma). The histological diagnosis must be obtained from a neurosurgical resection of the tumor or by an open biopsy (stereotactic biopsy not allowed).
3. Tumor tissue specimens from the GBM surgery or open biopsy (formalin-fixed paraffin-embedded [FFPE] block) must be available for MGMT gene promoter status analysis and central pathology review.
4. Proven unmethylated MGMT gene promoter status (i.e. cut-off ratio <1 by means of applied test to determine MGMT gene promoter status)
5. Males or females =18 years of age.
6. Interval of =2 weeks but =7 weeks after surgery or biopsy before first administration of study treatment.
7. Available post-operative Gd-MRI performed within <48 hours after surgery (in case that it was not possible to obtain a Gd-MRI within <48 hours post surgery, a Gd-MRI is to be performed prior to randomization).
8. Stable or decreasing dose of steroids for ‡5 days prior to randomization.
9. ECOG PS of 0-1.
10. Meets 1 of the following RPA classifications:
• Class III (Age <50 years and ECOG PS 0).
• Class IV (meeting one of the following criteria: a) Age <50 years and ECOG PS 1 or b) Age =50 years, underwent prior partial or total tumor resection, Mini Mental State Examination [MMSE] =27).
• Class V (meeting one of the following criteria: a) Age =50 years and underwent prior partial or total tumor resection, MMSE <27 or
b) Age =50 years and underwent prior tumor biopsy only).
11. 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) within normal limits and partial thromboplastin time (PTT) below upper limit of normal.
• 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) or transient increase post surgery attributable to narcotics).
• Alkaline phosphatase £2.5 x ULN.
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
1. Prior chemotherapy within the last 5 years.
2. Prior RTX of the head (except for low dose radiotherapy for Tinea capitis).
3. Receiving concurrent investigational agents or has received an investigational agent 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. Planned major surgery for other diseases
7. History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
8. 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.
9. History of coagulation disorder associated with bleeding or recurrent thrombotic events.
10. Clinically manifest myocardial insufficiency (New York Heart Association [NYHA] III, IV) or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension.
11. Inability to undergo Gd-MRI.
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 [b-HCG] test at screening) or is currently breast-feeding, or has the potential and 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. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Overall survival time;Secondary Objective: • Progression free survival time.<br>• Safety and tolerability of the combination of cilengitide with standard RTX and TMZ .<br>• PK profile of cilengitide when given daily (5 out of 7 days) at 2000 mg in combination with RTX and TMZ on days of RTX.;Primary end point(s): To investigate the overall survival (OS) time in subjects receiving 2 different regimens of 2000 mg cilengitide in combination with RTX and TMZ standard therapy.
- Secondary Outcome Measures
Name Time Method