search
Back to results

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

Primary Purpose

Glioblastoma Multiforme

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
bevacizumab and Irinotecan and radiotherapy
Bevacizumab and Temozolomide and radiotherapy
Sponsored by
Ulrik Lassen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Newly diagnosed patients with glioblastoma multiforme., Performance status 0-2.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Rigshospitalet
  • Odense Hospital
  • Århus Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

arm I

Arm II

Arm Description

Bevacizumab + Irinotecan and concomitant radiotherapy

Bevacizumab and Temozolomide and concomitant radiotherapy

Outcomes

Primary Outcome Measures

Objective response rate according to McDonald criteria

Secondary Outcome Measures

Progression-free survival

Full Information

First Posted
December 8, 2008
Last Updated
November 29, 2011
Sponsor
Ulrik Lassen
search

1. Study Identification

Unique Protocol Identification Number
NCT00817284
Brief Title
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

2. Study Status

Record Verification Date
November 2011
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ulrik Lassen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme
Keywords
Newly diagnosed patients with glioblastoma multiforme., Performance status 0-2.

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
arm I
Arm Type
Experimental
Arm Description
Bevacizumab + Irinotecan and concomitant radiotherapy
Arm Title
Arm II
Arm Type
Experimental
Arm Description
Bevacizumab and Temozolomide and concomitant radiotherapy
Intervention Type
Drug
Intervention Name(s)
bevacizumab and Irinotecan and radiotherapy
Intervention Description
Bevacizumab 10 mg/kg is administered on days 1 and 15. Irinotecan: Irinotecan 125 mg/m2 is administered on days 1 and 15 to patients NOT receiving enzyme-inducing antiepileptic drugs (EIAED). Irinotecan 340 mg/m2 is administered on days 1 and 15 to patients receiving EIAEDs. During concomitant chemoradiotherapy, bevacizumab and irinotecan are given in the same doses and schedules as before and after chemoradiotherapy. Radiotherapy is delivered during 3rd and 4th cycle of chemotherapy and consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday to Friday) over a period of six weeks for a total dose of 60 Gy.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab and Temozolomide and radiotherapy
Intervention Description
Bevacizumab 10 mg/kg is administered on days 1 and 15. Temozolomide dosing before start concomitant chemoradiotherapy: 150 mg/m2/day on days 1-5 during the first 28 days treatment cycle, then 200 mg/m2/day on the subsequent cycles until radiotherapy. Temozolomide administered concomitantly with the radiotherapy: Temozolomide 75 mg/m2/day for 7 days per week is administered on each day of radiotherapy. After completed chemoradiotherapy, temozolomide is dosed and administered as it was prior to start chemoradiotherapy, i.e. temozolomide 200 mg/m2/day on days 1-5 out of a 28 days schedule, taking into consideration any previous dose-reductions already made. Radiotherapy is delivered during 3rd and 4th cycle of chemotherapy and consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday to Friday) over a period of six weeks for a total dose of 60 Gy.
Primary Outcome Measure Information:
Title
Objective response rate according to McDonald criteria
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Rigshospitalet
City
Copenhagen
Country
Denmark
Facility Name
Odense Hospital
City
Odense
Country
Denmark
Facility Name
Århus Hospital
City
Århus
Country
Denmark

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs