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

This study has been terminated.
(Results of the phase III RTOG0525 trial made the manufacturer of cilengitide decide to end their support to the trial)
Sponsor:
Information provided by (Responsible Party):
Bart Neyns, Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier:
NCT01044225
First received: January 6, 2010
Last updated: March 21, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Drug: Cetuximab
Drug: Cilengitide EMD 121974
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Universitair Ziekenhuis Brussel:

Primary Outcome Measures:
  • the 1 year overall survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: September 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01044225

Locations
Belgium
Onze-Lieve-Vrouwziekenhuis
Aalst, Belgium, 9300
ZNA Middelheim
Antwerpen, Belgium, 2020
GHdC Charleroi
Charleroi, Belgium, 6000
ZOL Campus Sint-Jan
Genk, Belgium, 3600
UZ Gent
Gent, Belgium, 9000
UCL de Mont-Godinne
Yvoir, Belgium, 5530
Sponsors and Collaborators
Bart Neyns
Investigators
Principal Investigator: Bart Neyns UZ Brussel
  More Information

No publications provided

Responsible Party: Bart Neyns, MD PhD, Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT01044225     History of Changes
Other Study ID Numbers: 2009-012324-83
Study First Received: January 6, 2010
Last Updated: March 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Universitair Ziekenhuis Brussel:
newly diagnosed glioblastoma

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
Cetuximab
Temozolomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014