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

NCT00689221 | Completed Phase 3 Results DMC

• 3 other identifiers: EMD 121974-011EORTC 26071-220722007-004344-78
• Study Type: interventional
• Target: 545
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Glioblastoma

Keywords

newly diagnosed Glioblastoma (WHO Grade IV); Cilengitide; Temozolomide; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) Time

  The OS time is defined as the time (in months) from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.

  Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, Sep 2008 until cut-off date, (19 Nov 2012)

Secondary Outcomes (11)

• Progression Free Survival (PFS) Time - Investigator and Independent Read

  Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, Sep 2008 until cut-off date, (19 Nov 2012)

• Maximum Observed Plasma Concentration (Cmax)

  Day 1 of Week -1

• Time to Maximum Plasma Concentration (Tmax)

  Day 1 of Week -1

• Area Under the Plasma Concentration Curve From Time 0 to 6 Hours (AUC [0-6]) After Dose

  Day 1 of Week -1

• European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Sub-scale Scores

  Up to 50 months

Study Arms (2)

Cilengitide + Temozolomide + Radiotherapy

EXPERIMENTAL

Drug: Cilengitide; Drug: Temozolomide; Radiation: Radiotherapy

Temozolomide + Radiotherapy

ACTIVE COMPARATOR

Drug: Temozolomide; Radiation: Radiotherapy

Interventions

Cilengitide DRUG

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.

Cilengitide + Temozolomide + Radiotherapy

Temozolomide DRUG

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.

Cilengitide + Temozolomide + Radiotherapy; Temozolomide + Radiotherapy

Radiotherapy RADIATION

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.

Cilengitide + Temozolomide + Radiotherapy; Temozolomide + Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization \[WHO\] Grade IV)
• Proven methylated MGMT gene promoter methylation status
• 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)
• Stable or decreasing dose of steroids for greater than or equal to (\>=) 5 days prior to randomization
• Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1
• 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)

You may not qualify if:

• Prior chemotherapy within the last 5 years
• Prior RTX of the head
• Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide
• Prior systemic antiangiogenic therapy
• Placement of Gliadel® wafer at surgery
• Inability to undergo Gd-MRI.
• Planned surgery for other diseases
• History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment
• 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
• History of coagulation disorder associated with bleeding or recurrent thrombotic events
• Clinically manifest myocardial insufficiency (New York Heart Association \[NYHA\] III, IV) or history of myocardial infarction during the past 6 months; uncontrolled arterial hypertension

Sponsors & Collaborators

• EMD Serono: lead
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (2)

Please Contact U.S. Medical Information Located in

Rockland, Massachusetts, United States

Location

Please Contact the Merck KGaA Communication Center Located in

Darmstadt, Germany

Location

Related Publications (3)

• Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial Roger Stupp, Monika E Hegi, Thierry Gorlia, Sara C Erridge, James Perry, Yong-Kil Hong, Kenneth D Aldape, Benoit Lhermitte, Torsten Pietsch, Danica Grujicic, Joachim Peter Steinbach, Wolfgang Wick, Rafał Tarnawski, Do-Hyun Nam, Peter Hau, Astrid Weyerbrock, Martin J B Taphoorn, Chiung-Chyi Shen, Nalini Rao, László Thurzo, Ulrich Herrlinger, Tejpal Gupta, Rolf-Dieter Kortmann, Krystyna Adamska, Catherine McBain, Alba A Brandes, Joerg Christian Tonn, Oliver Schnell, Thomas Wiegel, Chae-Yong Kim, Louis Burt Nabors, David A Reardon, Martin J van den Bent, Christine Hicking, Andriy Markivskyy, Martin Picard, Michael Weller The Lancet Oncology 20 August 2014(Article in Press DOI: 10.1016/S1470-2045(14)70379-1)

  RESULT

• Seliger C, Oppong FB, Lefranc F, Chinot O, Stupp R, Nabors B, Gorlia T, Weller M; EORTC Brain Tumor Group. Association of antidepressant drug use with outcome of patients with glioblastoma. Int J Cancer. 2023 Apr 1;152(7):1348-1359. doi: 10.1002/ijc.34344. Epub 2022 Nov 17.

  PMID: 36346112 DERIVED

• Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D, Steinbach JP, Wick W, Tarnawski R, Nam DH, Hau P, Weyerbrock A, Taphoorn MJ, Shen CC, Rao N, Thurzo L, Herrlinger U, Gupta T, Kortmann RD, Adamska K, McBain C, Brandes AA, Tonn JC, Schnell O, Wiegel T, Kim CY, Nabors LB, Reardon DA, van den Bent MJ, Hicking C, Markivskyy A, Picard M, Weller M; European Organisation for Research and Treatment of Cancer (EORTC); Canadian Brain Tumor Consortium; CENTRIC study team. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1100-8. doi: 10.1016/S1470-2045(14)70379-1. Epub 2014 Aug 19.

  PMID: 25163906 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Cilengitide; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Roger Stupp, Prof. Dr.

  University of Lausanne Medical Center (CHUV)

  STUDY CHAIR

• Andriy Markivskyy, MD

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2008
• First Posted: June 3, 2008
• Study Start: September 1, 2008
• Primary Completion: November 1, 2012
• Study Completion: August 1, 2013
• Last Updated: November 4, 2014
• Results First Posted: November 4, 2014

Record last verified: 2014-10

Locations

US (1); DE (1)