Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor)
Condition: Glioblastoma Multiforme
MeSH terms: Glioblastoma
Intervention: Cilengitide 500 mg; Cilengitide 2000 mg
Intervention description: Subjects will receive 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.; Subjects will receive 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Brain cancer; Brain tumor

Summary:

      This study will investigate clinical activity, safety, and tolerability of the
      anti-angiogenic compound cilengitide (EMD 121974) in the treatment of first recurrence of
      glioblastoma multiforme (GBM).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent obtained before undergoing any study-related activities.

          -  Males or females 18 years of age or older who can be treated in an outpatient setting.

          -  Histologically proven GBM, which is recurrent or progressive following surgery or
             biopsy, external beam radiation therapy, and 1 previous regimen of systemic
             chemotherapy (Gliadel wafer therapy is not considered systemic chemotherapy).
             Malignancy is to be documented with a previous histopathological report.

          -  Subjects initially diagnosed with other conditions similar to GBM (such as anaplastic
             astrocytoma [AA] or low grade glioma) that subsequently progressed to histologically
             proven GBM and have had surgery or biopsy, external beam radiation therapy, and 1
             previous regimen of systemic chemotherapy for the original diagnosis are eligible if
             they meet all inclusion criteria.

          -  GBM recurring only in the contralateral hemisphere must be histologically confirmed by
             biopsy. GBM recurring bilaterally does not need to be histologically confirmed by
             biopsy (i.e., if recurrence is ipsilateral and contralateral).

          -  Archived tumor tissue specimens from the GBM surgery or biopsy must be available for
             central pathology review and exploratory analysis of angiogenic markers (e.g. αvβ3 and
             αvβ5 integrins).

          -  Measurable disease (solid contrast-enhancing lesion greater than or equal to (>=)1 cm
             in any dimension) evaluated by gadolinium-enhanced magnetic resonance imaging (Gd MRI)
             within 2 weeks prior to the first dose of EMD 121974.

          -  At least 12 weeks have elapsed since the last radiation treatment, and at least 4
             weeks have elapsed since the last chemotherapy dose (at least 6 weeks for
             nitrosourea-containing chemotherapy) prior to the first dose of EMD 121974.

          -  If the subject underwent recent surgery, status must be >=2 weeks post surgery or >=1
             week post biopsy, in stable condition, and maintained on a stable corticosteroid
             regimen for >=5 days prior to first dose of EMD 121974.

          -  Karnofsky Performance Score (KPS) of >=70%.

          -  Subjects with the potential for pregnancy or impregnating their partner must agree to
             follow acceptable methods of birth control to avoid conception during the study and
             for at least 6 months after receiving the last dose of study drug.

          -  Women of childbearing potential must have a negative pregnancy test at screening.

          -  Laboratory values (within 1 week prior to the first dose of EMD 121974, except for
             blood count and Prothrombin time (PT)/Partial thromboplastin time (PTT), which are to
             be within 72 hours of the first dose): Absolute neutrophil count >=1500/millimeter
             (mm)^3. Platelets >=100,000/mm^3. Creatinine less than or equal to (<=) 1.5
             milligram/deciliter (mg/dL) or creatinine clearance >=60 mL/min. Hematocrit >=30%.
             Prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits.
             Hemoglobin >=10 mg/dL. Total bilirubin <=1.5 times the upper limit of normal.
             Aspartate aminotransferase and alanine aminotransferase <=2.5 times above upper limit
             of normal.

          -  No more than 8 weeks have elapsed since recurrence was detected

        Exclusion Criteria:

          -  Prior radiation therapy greater than (>) 66 Gray.

          -  Subject anticipates undergoing elective surgery, dental extraction, or invasive dental
             procedures.

          -  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 EMD 121974.

          -  Prior antiangiogenic therapy.

          -  Placement of Gliadel wafer at surgery for recurrence.

          -  Unable to undergo Gd MRI.

          -  Current known alcohol dependence or drug abuse.

          -  Requiring concomitant chemotherapy.

          -  Treatment with a prohibited concomitant medication.

          -  Known hypersensitivity to the study treatment.

          -  Legal incapacity or limited legal capacity.