Cetuximab, Bevacizumab and Irinotecan for Patients With Malignant Glioblastomas - Full Text View

Sponsors and Collaborators:	Rigshospitalet, Denmark Aalborg Hospital Odense University Hospital
Information provided by:	Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:	NCT00463073

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 II

Drug Information available for: Irinotecan Irinotecan hydrochloride Bevacizumab Cetuximab

U.S. FDA Resources

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

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00463073

Locations

Denmark
Odense University Hospital
Odense, Denmark, 5000
Rigshospitalet
Copenhagen, Denmark, 2100
Aalborg University Hospital
Aalborg, Denmark, 9000

Sponsors and Collaborators

Rigshospitalet, Denmark

Aalborg Hospital

Odense University Hospital

Investigators

Principal Investigator:

Ulrik Lassen, MD., PH.D.

Rigshospitalet, Dept. of Oncology

More Information

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

Keywords provided by Rigshospitalet, Denmark:

Progressive primary Glioblastoma multiforme

Study placed in the following topic categories:

Neuroectodermal Tumors
Glioblastoma
Glioblastoma multiforme
Astrocytoma
Neoplasms, Germ Cell and Embryonal
Cetuximab

Irinotecan
Disease Progression
Neuroepithelioma
Bevacizumab
Glioma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Angiogenesis Inhibitors

Pharmacologic Actions
Neoplasms
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Neoplasms, Neuroepithelial
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009