Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status
Condition: Glioblastoma
MeSH terms: Glioblastoma
Intervention: Cilengitide; Temozolomide; Radiotherapy
Intervention description: Cilengitide 2000 milligram (mg) will be administered intravenously twice weekly over 1 hour infusion from Weeks -1 to 77 or until occurrence of progressive disease, unacceptable toxicity, or withdrawal for any other reason. If considered beneficial in the opinion of the Investigator, continuation of cilengitide treatment will be optional in subjects without disease progression and after Week 77 since start of treatment.; Temozolomide (TMZ) 75 milligram per square meter [mg/m^2] will be administered intravenously once daily from Weeks 1 to 6. From Week 11 onwards, TMZ will be given as maintenance treatment at a dose of 150-200 mg/m^2 for consecutive 5 days every 4 weeks until Week 34 or until disease progression.; Radiotherapy (RTX) at a dose of 2 gray (Gy) per fraction will be given once daily, 5 days per week from Weeks 1 to 6, total dose 60 Gy.
Intervention MeSH terms: Temozolomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 545.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: newly diagnosed Glioblastoma (WHO Grade IV); Cilengitide; Temozolomide; Radiotherapy

Summary:

      CENTRIC is a Phase 3 clinical trial assessing efficacy and safety of the investigational
      integrin inhibitor, cilengitide, in combination with standard treatment versus standard
      treatment alone in newly diagnosed glioblastoma subjects with a methylated
      O6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) gene promoter in the tumor
      tissue.

      The MGMT gene promoter is a section of deoxyribonucleic acid (DNA) that acts as a controlling
      element in the expression of MGMT. Methylation of the MGMT gene promoter has been found to be
      a predictive marker for benefit from temozolomide (TMZ) treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Tumor tissue specimens from the glioblastoma surgery or open biopsy (formalin-fixed,
             paraffin-embedded block; stereotactic biopsy not allowed) must be available for MGMT
             status analysis and central pathology review

          2. Newly diagnosed histologically proven supratentorial glioblastoma (World Health
             Organization [WHO] Grade IV)

          3. Proven methylated MGMT gene promoter methylation status

          4. Available post-operative gadolinium-enhanced magnetic resonance imaging (Gd-MRI)
             performed within less than (<) 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)

          5. Stable or decreasing dose of steroids for greater than or equal to (>=) 5 days prior
             to randomization

          6. Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1

          7. Meets 1 of the following recursive partitioning analysis (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)

          8. Other protocol defined inclusion criteria could apply

        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
             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. Inability to undergo Gd-MRI.

          7. Planned surgery for other diseases

          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 (New York Heart Association [NYHA] III,
             IV) or history of myocardial infarction during the past 6 months; uncontrolled
             arterial hypertension

         12. Other protocol defined exclusion criteria could apply