Bevacizumab and Irinotecan or Bevacizumab and Temozolomide With Concomitant Radiotherapy for Primary Glioblastoma Multiforme (GBM)

Ulrik Lassen

Status and phase

Completed

Phase 2

Conditions

Glioblastoma Multiforme

Treatments

Drug: bevacizumab and Irinotecan and radiotherapy

Drug: Bevacizumab and Temozolomide and radiotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT00817284

BIBT-01

Details and patient eligibility

About

Significant activity (radiographic response rates of approximately 60%) has recently been demonstrated in phase II studies in patients with relapsed GBM from the combined use of Irinotecan (CPT-11) and bevacizumab. The 6-month progression-free survival rate is 30% and median survival duration is 9 months. The current first line therapy of GBM patients following initial surgical resection/debulking is the concomitant use of cerebral radiotherapy and the orally available alkylating agent temozolomide, followed by temozolomide for 6 months post-radiotherapy.

Considering the significant activity of the combination of Bevacizumab + irinotecan in patients with recurrent GBM, and considering the activity of temozolomide in GBM, it is proposed that the combination of Bevacizumab + Temozolomide may also be an active regimen. Bevacizumab + Temozolomide display non-overlapping toxicity clinically and thus their combined use without significant dose-reductions seems rational.

The toxicity from the combined use of the two drugs prior to radiotherapy, as well as the toxicity when administered together with radiotherapy, is evaluated.

This study will try to identity whether Bevacizumab and Irinitecan or Bevacizumab and Temozolomide should be the experimental arm in future phase III comparison with standard care with concomitant Temozolomide and radiotherapy.

Enrollment

60 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed informed consent
Histological verified primary glioblastoma multiforme
No prior therapy for GBM, except for primary surgical resection or biopsy
PS 0-2
Age > 18
Expected survival > 3 months
Adequate liver, renal and bone-marrow function, determined as:
- Thrombocytes > 100 x 109/liter
- Hemoglobin >6.2 mmol/liter
- Leukocytes > 3 x 109/liter
- Neutrophil granulocytes > 1.5 x 109/liter
- ASAT and/or ALAT < 3 x upper normal limit
- Bilirubin < 1.5 x upper normal limit
- Serum-creatinin < upper normal limit or glomerular filtration rate >60 ml/min (corrected for age) determined by measurement of clearance of Cr-EDTA
- APTT < upper normal limit
- INR < upper normal limit
Fertile women of childbearing age must use proper anti-conception (oral contraceptives, IUD and/or condom). Fertile men must use condom
No sign of cerebral bleeding on cerebral MR-scanning at baseline.

Exclusion criteria

Previous therapy of GBM, including radiotherapy and the use of biological " targeted" drug, e.g. drugs targeted against the VEGF- or EGFR pathway
Concurrent use of medication that can affect the interpretation of the results from the study, e.g. use of immunosuppressive drugs, except corticosteroids
Conditions (medical, social or physical) that may compromise proper information and/or follow-up
Other concurrent or previous cancer within 5 years, except adequately treated basal or planocellular skin cancer, or cervical carcinoma in situ
Significant heart disease (according to the New York Heart Association class II or more severe), clinically significant arrhythmia or unstable angina pectoris/acute myocardial infarction within last 6 months
Clinical significant peripheral arterial disease
Known or suspected disorders of coagulation or concurrent therapy with ASA, NSAID or clopidogrel
Major surgery, open biopsy or greater trauma, or expectations thereof, within 28 days prior to start of therapy
Minor surgery or needle biopsy, or expectations thereof, within 7 days prior to start of therapy
Known or suspected abdominal fistulas, gastrointestinal perforations or intra-abdominal abscesses within 6 months prior to start of therapy
Chronic inflammatory intestinal disease and/or intestinal obstruction
Known or active HIV or Hepatitis B/C infection
Concurrent ongoing significant infection or diabetes mellitus not adequately controlled medically
Clinically significant non-healing ulcers
Active ventricular or duodenal ulcers within 6 months prior to start of therapy
Recent bone-fracture (<3 months)
Pregnancy or lactation
Need for systemic anticoagulant therapy at time of start of therapy
Blood pressure > 150/100 mmHg (patients are allowed to receive proper antihypertensive medication)
Proteinuria ≥ 1 gram/day
Known allergy toward irinotecan (or related substance) or vehicle
Known allergy toward temozolomide (or related substance) or vehicle
Known allergy toward bevacizumab (or related substance) or vehicle