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

Sponsor:	EMD Serono
Collaborator:	European Organization for Research and Treatment of Cancer - EORTC
Information provided by:	EMD Serono
ClinicalTrials.gov Identifier:	NCT00689221

Purpose

CENTRIC is a Phase III 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 multiforme (GBM) patients with a methylated promoter of the methylguanine-DNA methyltransferase (MGMT) gene in the tumor tissue.

The MGMT gene promoter is a section of 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, Temozolomide & Radiotherapy Drug: Temozolomide & Radiotherapy	Phase III

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 Multiforme 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

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Cilengitide

U.S. FDA Resources

Further study details as provided by EMD Serono:

Primary Outcome Measures:

Overall Survival [ Time Frame: various timepoints ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and tolerability, PFS, QoL and population PK [ Time Frame: various timepoints ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	504
Study Start Date:	September 2008
Estimated Study Completion Date:	October 2016
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Cilengitide, Radiotherapy & Temozolomide	Drug: Cilengitide, Temozolomide & Radiotherapy Cilengitide 2000mg i.v. twice weekly, Temozolomide & Radiotherapy
2 Temozolomide & Radiotherapy	Drug: Temozolomide & Radiotherapy Temozolomide & Radiotherapy

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Tumor tissue specimens from the GBM 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 GBM (World Health Organization [WHO] Grade IV).
Proven methylated MGMT gene promoter methylation status.
Available post-operative Gd-MRI performed within <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 ³5 days prior to randomization
ECOG PS of 0-1.
Meets 1 of the following 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, 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).

Exclusion Criteria:

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 (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 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 ³ 5 years are eligible for this study.
History of coagulation disorder associated with bleeding or recurrent thrombotic events.
Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial infarction during the past 6 months. Uncontrolled arterial hypertension.

Contacts and Locations

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

Locations

United States, Massachusetts
Central US Contact Local Medical Information Office located in
Rockland, Massachusetts, United States
Germany
Central EU Contact Merck KGaA Communication Center located in
Darmstadt, Germany

Sponsors and Collaborators

EMD Serono

European Organization for Research and Treatment of Cancer - EORTC

Investigators

Study Chair:

Roger Stupp, Dr. med.

Centre pluridisciplinaire d'Oncologie

More Information

No publications provided

Responsible Party:	Dr. Martin Picard, Merck KGaA
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:	July 13, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by EMD Serono:

newly diagnosed Glioblastoma (WHO Grade IV)

Additional relevant MeSH terms:

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

Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012