Effect of Radiation Therapy Plus Temozolomide Combined With Cilengitide or Cetuximab on the 1-year Overall Survival of Patients With Newly Diagnosed MGMT-promoter Unmethylated Glioblastoma

NCT01044225 | Terminated Phase 2 DMC

• 1 other identifier: 2009-012324-83
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief Summary

The investigators propose to conduct a multicenter, open-label, randomized, phase II study in patients with newly diagnosed glioblastoma (CeCil). Patients should meet all eligibility criteria for the CENTRIC phase III trial at the exception that no MGMT-promoter methylation could be demonstrated. The treatment backbone in both study arms will consist of postoperative radiation therapy with concomitant daily temozolomide, followed by 6 cycles of temozolomide according to a 21 out of 28 days regimen (as in the experimental arm of the RTOG 0525 / EORTC 26052-22053 phase III study). In study arm (A) Cilengitide (at a dose of 2000 mg by iv administration, 2x/week) will be added to this backbone while in the second study arm (B), Cetuximab will be added (at an initial dose of 400 mg/m² administered by intravenous infusion over 2 hours and followed by a weekly dose of 250 mg/m² iv over 1 hours). In both study arms, treatment will be administered for 52 consecutive treatment weeks. The 1-year overall survival (1y-OS) following randomization will serve as the primary endpoint in both study arms.

Conditions

Glioblastoma

Keywords

newly diagnosed glioblastoma

Outcome Measures

Primary Outcomes (1)

• the 1 year overall survival

  1 year

Study Arms (2)

Cilengitide EMD 121974

ACTIVE COMPARATOR

A dose of 2000 mg by iv administration 2 weekly.

Drug: Cilengitide EMD 121974

Cetuximab

ACTIVE COMPARATOR

An initial dose of 400 mg/m² IV over 2 hours and followed by a weekly dose of 250 mg/m² over 1 hour.

Drug: Cetuximab

Interventions

Cetuximab DRUG

An initial dose of 400 mg/m² IV over 2 hours and followed by a weekly dose of 250 mg/m² over 1 hour.

Cetuximab

Cilengitide EMD 121974 DRUG

A dose of 2000 mg by IV administration 2 weekly.

Cilengitide EMD 121974

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization \[WHO\] Grade IV, including glioblastoma subtypes, e.g. gliosarcoma).
• Tumor tissue specimens from the glioblastoma surgery or open biopsy (FFPE block) must be available for MGMT gene promoter status analysis and central pathology review and must have been submitted as part of the screen procedure for the CENTRIC phase III study
• MGMT gene promoter status determined as NOT methylated during the screen procedure for the CENTRIC phase III study
• Males or females ≥18 years of age.
• Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
• Available post-operative 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 score (ECOG PS) of 0-1.
• Meets one 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 open tumor biopsy only).
• Laboratory values
• Absolute neutrophil count 1500/mm3.

You may not qualify if:

• Prior chemotherapy within the last 5 years.
• Prior RT 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 anti-angiogenic therapy.
• Placement of Gliadel® wafer at surgery.
• Planned surgery for other diseases (e.g. dental extraction).
• History of recent peptic ulcer disease 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 or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension.
• Inability to undergo Gd-MRI.
• Concurrent illness, including severe dermatological conditions or infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
• Subject is pregnant 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 pessary, 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

• Bart Neyns: lead

Study Sites (6)

Onze-Lieve-Vrouwziekenhuis

Aalst, Aalst, 9300, Belgium

Location

ZNA Middelheim

Antwerp, Antwerpen, 2020, Belgium

Location

GHdC Charleroi

Charleroi, Charleroi, 6000, Belgium

Location

ZOL Campus Sint-Jan

Genk, 3600, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UCL de Mont-Godinne

Yvoir, 5530, Belgium

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Cetuximab; Cilengitide

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bart Neyns

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: January 6, 2010
• First Posted: January 7, 2010
• Study Start: September 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: March 22, 2012

Record last verified: 2012-03

Locations

BE (6)