Clinical trial NCT00817284: Bevacizumab and Irinotecan or Bevacizumab and Temozolomide With Concomitant Radiotherapy for Primary Glioblastoma Multiforme (GBM)
Official title: A Randomized Phase II Trial With Bevacizumab, Irinotecan and Cerebral Radiotherapy Versus Bevacizumab, Temozolomide and Cerebral Radiotherapy as First Line Treatment for Patients With Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Newly diagnosed patients with glioblastoma multiforme.
Performance status 0-2.
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2009-01-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate according to McDonald criteria
timeFrame: 6 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense Hospital
city: Århus
country: Denmark
facility: Århus Hospital
Study officials:
References: