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

March 21, 2012 updated by: Bart Neyns

CeCil: A Randomized, Non-comparative Clinical Trial of the 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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Aalst, Belgium, 9300
        • Onze-Lieve-Vrouwziekenhuis
      • Antwerpen, Belgium, 2020
        • Zna Middelheim
      • Charleroi, Belgium, 6000
        • GHdC Charleroi
      • Genk, Belgium, 3600
        • ZOL Campus Sint-Jan
      • Gent, Belgium, 9000
        • Uz Gent
      • Yvoir, Belgium, 5530
        • Ucl de Mont-Godinne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Written informed consent
  2. Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization [WHO] Grade IV, including glioblastoma subtypes, e.g. gliosarcoma).
  3. 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
  4. MGMT gene promoter status determined as NOT methylated during the screen procedure for the CENTRIC phase III study
  5. Males or females ≥18 years of age.
  6. Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
  7. Available post-operative Gd-MRI performed within 48 hours after surgery
  8. Stable or decreasing dose of steroids for 5 days prior to randomization.
  9. Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1.

  10. 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).

  11. Laboratory values

    • Absolute neutrophil count 1500/mm3.
    • Platelets 100,000/mm3.
    • Creatinin 1.5 x upper limit of normal (ULN) or creatinine clearance rate 60 mL/min.
    • Hemoglobin 10 g/dL.
    • Total bilirubin 1.5 x the ULN.
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2.5 x ULN (except when attributable to anticonvulsants).
    • Alkaline phosphatase 2.5 x ULN.
    • Prothrombin time (PT) international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits.

Exclusion Criteria:

  1. Prior chemotherapy within the last 5 years.
  2. Prior RT 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 anti-angiogenic therapy.
  5. Placement of Gliadel® wafer at surgery.
  6. Planned surgery for other diseases (e.g. dental extraction).
  7. History of recent peptic ulcer disease within 6 months of enrollment.
  8. 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.
  9. History of coagulation disorder associated with bleeding or recurrent thrombotic events.
  10. Clinically manifest myocardial insufficiency or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension.
  11. Inability to undergo Gd-MRI.
  12. 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.
  13. 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.
  14. Current alcohol dependence or drug abuse.
  15. Known hypersensitivity to the study treatment.
  16. Legal incapacity or limited legal capacity.
  17. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  18. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
  19. Treatment with prohibited concomitant medication as defined in Section

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Cilengitide EMD 121974
A dose of 2000 mg by iv administration 2 weekly.
Drug: Cilengitide EMD 121974
A dose of 2000 mg by IV administration 2 weekly.
ACTIVE_COMPARATOR: Cetuximab
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
An initial dose of 400 mg/m² IV over 2 hours and followed by a weekly dose of 250 mg/m² over 1 hour.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
the 1 year overall survival
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bart Neyns

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Bart Neyns, Universitair Ziekenhuis Brussel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2009

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2011

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 6, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 6, 2010

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 7, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 22, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 21, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2009-012324-83

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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