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

NCT00813943 | Completed Phase 2 Results

• 1 other identifier: EMD121974-012
• Study Type: interventional
• Target: 265
• Locations: 2 countries
• Sites: 2

Brief Summary

CORE is a Phase 2 clinical trial in newly diagnosed glioblastoma in subjects with an unmethylated 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 appear to be a predictive marker for benefit from temozolomide (TMZ) treatment. In a safety run-in period in dedicated study centers, the safety and tolerability of Cilengitide given as an intense treatment in combination with the first part of standard therapy will be assessed. Thereafter the trial will investigate the overall survival and progression-free survival in subjects receiving two different regimens of Cilengitide in combination with standard treatment versus standard treatment alone.

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, Jun 2009 until cut-off date, (07 Feb 2013)

Secondary Outcomes (12)

• 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, Jun 2009 until cut-off date, (07 Feb 2013)

• Maximum Observed Plasma Concentration (Cmax)

  Days 1 and 5 of Week 1

• Time to Maximum Plasma Concentration (Tmax) and Terminal Elimination Half-Life (t1/2)

  Days 1 and 5 of Week 1

• Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) and Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24])

  Days 1 and 5 of Week 1

• Plasma Concentration at Pre-dose (Cpre) and Plasma Concentration at End of Infusion (CT)

  Days 1 and 5 of Week 1

Study Arms (3)

Cilengitide (2-times weekly) + Temozolomide + Radiotherapy

EXPERIMENTAL

Drug: Cilengitide (2-times weekly); Drug: Temozolomide; Radiation: Radiotherapy

Cilengitide (5-times weekly) + Temozolomide + Radiotherapy

EXPERIMENTAL

Drug: cilengitide (5-times weekly); Drug: Temozolomide; Radiation: Radiotherapy

Temozolomide + Radiotherapy

ACTIVE COMPARATOR

Drug: Temozolomide; Radiation: Radiotherapy

Interventions

Cilengitide (2-times weekly) 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 (2-times weekly) + Temozolomide + Radiotherapy

cilengitide (5-times weekly) DRUG

Cilengitide 2000 milligram (mg) will be administered intravenously 5-times 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 (5-times weekly) + Temozolomide + Radiotherapy

Temozolomide DRUG

Temozolomide (TMZ) 75 milligram per square meter \[mg/m\^2\] will be administered intravenously once daily from Week 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 (2-times weekly) + Temozolomide + Radiotherapy; Cilengitide (5-times weekly) + Temozolomide + Radiotherapy; Temozolomide + Radiotherapy

Radiotherapy RADIATION

Radiation therapy (RTX) at a dose of 2 gray (Gy) per fraction will be given once daily, 5 days per week from Week 1 to 6, total dose 60 Gy.

Cilengitide (2-times weekly) + Temozolomide + Radiotherapy; Cilengitide (5-times weekly) + 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:

• Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization \[WHO\] Grade IV, including glioblastoma subtypes, for example, gliosarcoma). The histological diagnosis has to be obtained from a neurosurgical resection of the tumor or by an open biopsy (stereotactic biopsy is not allowed)
• Tumor tissue specimens from the glioblastoma surgery or open biopsy (formalin-fixed paraffin-embedded) must be available for MGMT gene promoter status analysis and central pathology review
• Proven unmethylated MGMT gene promoter status (that is, cut-off ratio less than (\<) 2 by means of applied test to determine MGMT gene promoter status)
• Males or females greater than or equal to (\>=) 18 years of age
• Interval of \>= 2 weeks but less than or equal to (=\<) 7 weeks after surgery or biopsy before first administration of study treatment
• Available post-operative gadolinium-enhanced magnetic resonance imaging (Gd-MRI) performed within \< 48 hours after surgery
• Stable or decreasing dose of steroids for \>= 5 days prior to randomization
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
• Has to meet 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 (except for low dose RTX for tinea capitis)
• Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of cilengitide
• Prior systemic anti-angiogenic therapy
• Placement of Gliadel® wafer at surgery
• 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; or uncontrolled arterial hypertension
• Inability to undergo Gd-MRI
• Concurrent illness, including severe infection (for example, human immunodeficiency virus), which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety
• Subject is pregnant (positive serum beta human chorionic gonadotropin \[b-HCG\] test at screening) or is currently breast-feeding, anticipates becoming pregnant/impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment
• Current alcohol dependence or drug abuse
• Known hypersensitivity to the study treatment

Sponsors & Collaborators

• EMD Serono: lead
• 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 (1)

• 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

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

• Andriy Markivskyy, MD

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

• Louis B. Nabors, Prof. Dr.

  University of Alabama at Birmingham

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2008
• First Posted: December 23, 2008
• Study Start: March 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: August 1, 2013
• Last Updated: January 30, 2017
• Results First Posted: December 8, 2014

Record last verified: 2017-01

Locations

DE (1); US (1)