Cetuximab, Bevacizumab and Irinotecan for Patients With Malignant Glioblastomas

This study has been completed.
Sponsor:
Collaborators:
Aalborg Universitetshospital
Odense University Hospital
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00463073
First received: April 19, 2007
Last updated: December 10, 2008
Last verified: December 2008
  Purpose

Irinotecan has demonstrated activity in malignant gliomas in multiple phase II studies. The activity is limited, with an approximately 15 % response rate and a progression-free survival of 3-5 months. Given the synergy between irinotecan and bevacizumab in colorectal cancer, and the high-level expression of vascular endothelial growth factor on malignant gliomas, one would expect synergy between bevacizumab and irinotecan against gliomas. In addition, 40-50 % of GBM have EGFR amplification/mutation making the EGFR an additional target. By combing cetuximab, with irinotecan and bevacizumab, one would expect further response, than irinotecan and bevacizumab alone. In addition, recurrent gliomas have an extremely poor prognosis, so innovative therapies are needed.


Condition Intervention Phase
Malignant Gliomas
Drug: Cetuximab
Drug: Bevacizumab
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase II Trial With Cetuximab, Bevacizumab and Irinotecan for Patients With Malignant Glioblastomas and Progression After Radiation Therapy and Temozolamide

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Enrollment: 32
Study Start Date: August 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
  Eligibility

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

Inclusion Criteria:

  • Written informed consent
  • Histological verification of primary GBM
  • Recurrence or progression after standard treatment (debulking surgery of possible, radiotherapy and temozolamide within last six months)
  • Evidence of measurable recurrent progressive primary GBM (CT/MRI scan)
  • PS 0-2 (ECOG scale)
  • Age > 18
  • Life expectancy > 3 month
  • Normal organ function:
  • Platelets > 125 x 109/l
  • Hemoglobin >6,2 mmol/l
  • Leukocytes > 3 x 109/l
  • ACN> 1,5 x 109/l
  • ASAT and/or ALAT < 3 x upper normal limit
  • Bilirubin < 1,5 x upper normal limit
  • Creatinine clearance > 45 ml/min
  • Creatinine < 1,5 x upper normal limit
  • APTT < normal limit
  • INR < normal limit
  • Cholesterol < 7 mmol/l
  • Fertile females must use oral contraceptive, IUD (intrauterine device) or preservatives. Fertile males must use preservatives.

Exclusion criteria:

  • Radiotherapy or chemotherapy within the last 4 weeks.
  • Co-medication that may interfere with study results; e.g. immunosuppressive agents other than corticosteroids
  • Prior EGFR- or VEGFR- based therapy.
  • Any condition (medical, social, psychological), which would prevent adequate information and follow-up
  • Any other active malignancy or previous malignancies within the last 5 years, except, adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ.
  • No hypercholesterolemia or hypertriglyceridemia (despite lipid-lowering therapy).
  • Any significant cardiac disease (New York Heart Association Class II or greater), arrhythmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris.
  • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis, coagulapathy or taking ASA, NSAIDs or clopidogrel
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the curse of the study
  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to day 0
  • History of known HIV, Hepatitis B and Hepatitis C negative
  • Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound, ulcer or bone fracture
  • Pregnancy or breast feeding
  • Requires therapeutic anti-coagulation
  • Blood pressure > 150/100 mmHG
  • Grade 2 or greater proteinuria
  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: NCT00463073

Locations
Denmark
Aalborg University Hospital
Aalborg, Denmark, 9000
Rigshospitalet
Copenhagen, Denmark, 2100
Odense University Hospital
Odense, Denmark, 5000
Sponsors and Collaborators
Rigshospitalet, Denmark
Aalborg Universitetshospital
Odense University Hospital
Investigators
Principal Investigator: Ulrik Lassen, MD., PH.D. Rigshospitalet, Dept. of Oncology
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00463073     History of Changes
Other Study ID Numbers: CBI-GBM-01
Study First Received: April 19, 2007
Last Updated: December 10, 2008
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Rigshospitalet, Denmark:
Progressive primary Glioblastoma multiforme

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Cetuximab
Irinotecan
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014