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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00817284
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Ulrik Lassen
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Completed
Countries Denmark
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma Multiforme
Arms & Interventions

Arms

Experimental: arm I

Bevacizumab + Irinotecan and concomitant radiotherapy

Experimental: Arm II

Bevacizumab and Temozolomide and concomitant radiotherapy

Interventions

Drug: - bevacizumab and Irinotecan and radiotherapy

- 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.

Drug: - Bevacizumab and Temozolomide and radiotherapy

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Rigshospitalet, Copenhagen, Denmark

Status

Address

Rigshospitalet

Copenhagen, ,

Odense Hospital, Odense, Denmark

Status

Address

Odense Hospital

Odense, ,

Århus Hospital, Århus, Denmark

Status

Address

Århus Hospital

Århus, ,