Cilengitide (EMD121974) and temozolomide with concomitant radiation therapy, followed by cilengitide and temozolomide maintenance therapy in subjects with newly diagnosed glioblastoma multiforme – a multicenter, open-label, uncontrolled Phase I/IIa study

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 50

Inclusion Criteria

- Written informed consent obtained before undergoing any study-related activities
- Males or females = 18 to < 70 years of age.
- Newly diagnosed, histologically proven supratentorial GB (WHO Grade IV). The histological diagnosis can be obtained either from a brain biopsy or from a neurosurgical resection of the tumor.
- Interval of = 3 weeks but = 5 weeks since surgery or biopsy before enrollment.
- For subjects who had undergone a tumor biopsy, disease evaluated by Gd-MRI within 1 week prior to the first dose of cilengitide.
- For subjects who had undergone tumor resection or debulking, availability of a postoperative Gd-MRI performed within < 48 hours after surgery. (In the exceptional case that it was not possible to obtain a Gd-MRI within 48 hours post surgery, and upon receiving confirmation from the central registration desk, a Gd-MRI is to be performed within 1 week prior to the start of cilengitide treatment.)
- Tumor tissue specimens from the GB surgery (paraffin-embedded and fresh-frozen) or biopsy (paraffin-embedded and, if available, fresh frozen) must be available for central pathology review and analysis of molecular markers relevant for this study (avb3 and avb5 integrins and MGMT gene methylation status).
- No prior chemotherapy in the last 5 years.
- No prior RT of the head.
- Stable or decreasing dose of steroids for = 8 days.
- Eastern Cooperative Oncology Group performance status (ECOG PS) = 2.
- Women of childbearing potential must have a negative pregnancy test at screening.
- Subjects with the potential for pregnancy or impregnating their partner must agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar (IUP) or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study drug.
- Laboratory values (within 1 week prior to the first dose of cilengitide):
Absolute neutrophil count =1500/mm³.
Platelets = 100,000/mm³.
Creatinine = 1.5 times upper limit of normal (ULN) or creatine clearance rate = 60 mL/min.
PT international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits.
Hemoglobin =10 mg/dL.
Total bilirubin = 1.5 times the ULN.
Aspartate aminotransferase and alanine aminotransferase = 2.5 times above ULN.
Alkaline phosphatase = 2.5 times above ULN.
- Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG) measured during screening. No history of stroke.

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

Exclusion Criteria

- Planned surgery for other diseases (e. g., dental extraction).
- History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
- History of prior 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.
- History of coagulation disorder associated with bleeding or recurrent thrombotic events.
- Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
- Subject is pregnant, anticipates becoming pregnant within 6 months after study participation, or is currently breast-feeding.
- Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide.
- Prior antiangiogenic therapy.
- Placement of Gliadel® wafer at surgery.
- Unable to undergo Gd-MRI.
- Current alcohol dependence or drug abuse.
- Treatment with a prohibited concomitant medication (see Section 6.9.1).
- Known hypersensitivity to the study treatment.
- Legal incapacity or limited legal capacity.
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before enrollment in the trial.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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