Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status (CENTRIC)

This study has been completed.
Sponsor:
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Merck KGaA
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00689221
First received: May 29, 2008
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

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 promoter of the O6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) gene 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.


Condition Intervention Phase
Glioblastoma
Drug: Cilengitide
Drug: Temozolomide
Radiation: Radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cilengitide for Subjects With Newly Diagnosed Glioblastoma and Methylated MGMT Gene Promoter - A Multicenter, Open-label, Controlled Phase III Study, Testing Cilengitide in Combination With Standard Treatment (Temozolomide With Concomitant Radiation Therapy, Followed by Temozolomide Maintenance Therapy) Versus Standard Treatment Alone (CENTRIC)

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Overall Survival Time [ Time Frame: follow up to 48 months after trial initiation ] [ Designated as safety issue: No ]
    Overall survival time will be measured from randomization to the date of death.


Secondary Outcome Measures:
  • Progression free survival (PFS) time [ Time Frame: follow up to 48 months after trial initiation ] [ Designated as safety issue: No ]
    PFS will be measured from randomization to the first evidence of progressive disease (PD) or occurrence of death due to any cause.

  • Population Pharmacokinetics parameter: Maximum observed plasma concentration (Cmax) [ Time Frame: Day 1 of Week -1, 7 and 11 ] [ Designated as safety issue: No ]
  • Population Pharmacokinetics parameter: Time to maximum plasma concentration (Tmax) [ Time Frame: Day 1 of Week -1, 7 and 11 ] [ Designated as safety issue: No ]
  • Population Pharmacokinetic parameter: Area under the plasma concentration curve, time 0 to infinity (AUC [0-infinity]) [ Time Frame: Day 1 of Week -1, 7 and 11 ] [ Designated as safety issue: No ]
  • Number of subjects with adverse events belonging to Standardized MedDRA Queries (SMQs) thromboembolic event and hemorrhages with National Cancer Institute-Common Toxicity Criteria (NCI−CTC) toxicity Grade 3 or 4 [ Time Frame: Screening up to 28 days after the last dose of study treatment ] [ Designated as safety issue: Yes ]
  • Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 [ Time Frame: Screening, Day 1 of Week 3, 6, 10, 18, 26, 34 thereafter every 12 weeks until progressive disease or withdrawal for any reason ] [ Designated as safety issue: No ]
  • Quality of Life Assessment (EORTC QLQ-BN20) [ Time Frame: Screening, Day 1 of Week 3, 6, 10, 18, 26, 34 thereafter every 12 weeks until progressive disease or withdrawal for any reason ] [ Designated as safety issue: No ]
  • Quality of Life (QoL) Assessed by EuroQol 5-Dimensions (EQ-5D) Questionnaire [ Time Frame: Screening, Day 1 of Week 3, 6, 10, 18, 26, 34 thereafter every 12 weeks until progressive disease or withdrawal for any reason ] [ Designated as safety issue: No ]
  • Health Care Resource Utilization and work status [ Time Frame: Screening, Day 1 of Week 3, 6, 10, 18, 26, 34 thereafter every 12 weeks until progressive disease or withdrawal for any reason ] [ Designated as safety issue: No ]
  • Number of subjects with adverse events (AEs), Serious AEs, treatment emergent AEs, AEs leading to death, and AEs with NCI−CTC toxicity Grade 3 or 4 [ Time Frame: Screening up to 28 days after the last dose of study treatment ] [ Designated as safety issue: Yes ]
  • Number of subjects with clinically significant abnormal Electrocardiogram (ECG) and lab parameters [ Time Frame: Screening up to 28 days after the last dose of study treatment ] [ Designated as safety issue: Yes ]

Enrollment: 545
Study Start Date: September 2008
Study Completion Date: August 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cilengitide + Temozolomide + Radiotherapy Drug: Cilengitide
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.
Drug: Temozolomide
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.
Radiation: Radiotherapy
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.
Active Comparator: Temozolomide + Radiotherapy Drug: Temozolomide
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.
Radiation: Radiotherapy
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00689221

Locations
United States, Massachusetts
Please Contact U.S. Medical Information Located in
Rockland, Massachusetts, United States
Germany
Please Contact the Merck KGaA Communication Center Located in
Darmstadt, Germany
Sponsors and Collaborators
EMD Serono
European Organisation for Research and Treatment of Cancer - EORTC
Merck KGaA
Investigators
Study Chair: Roger Stupp, Prof. Dr. University of Lausanne Medical Center (CHUV)
Study Director: Andriy Markivskyy, MD Merck KGaA
  More Information

No publications provided by EMD Serono

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00689221     History of Changes
Other Study ID Numbers: EMD 121974-011, EORTC 26071-22072
Study First Received: May 29, 2008
Last Updated: September 24, 2013
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by EMD Serono:
newly diagnosed Glioblastoma (WHO Grade IV)
Cilengitide
Temozolomide
Radiotherapy

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014