Glioblastoma MultiformePhase 2NCT00817284
Bevacizumab and Irinotecan or Bevacizumab and Temozolomide With Concomitant Radiotherapy for Primary Glioblastoma Multiforme (GBM)
A Phase 2 study testing bevacizumab and Irinotecan and radiotherapy and Bevacizumab and Temozolomide and radiotherapy in people with Glioblastoma Multiforme, run by Ulrik Lassen at 3 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- bevacizumab and Irinotecan and radiotherapy and Bevacizumab and Temozolomide and radiotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesDenmark
- Study dates
- Nov 2008to Nov 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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.
Who cannot join
- 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
Show all 23Show fewer
- 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 locations and contacts
3 sites in 1 country.
Denmark3 sites
Århus Hospital
Aarhus
Rigshospitalet
Copenhagen
Odense Hospital
Odense
About this study
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
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.
Read more
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.
- Conditions
- Glioblastoma Multiforme
- Being tested
- bevacizumab and Irinotecan and radiotherapy, Bevacizumab and Temozolomide and radiotherapy
- Keywords
- Newly diagnosed patients with glioblastoma multiforme., Performance status 0-2.
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumab and Irinotecan and radiotherapyDrug
- 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.
Bevacizumab and Temozolomide and radiotherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| arm I | Experimental | Bevacizumab + Irinotecan and concomitant radiotherapy Receives: Drug: bevacizumab and Irinotecan and radiotherapy |
| Arm II | Experimental | Bevacizumab and Temozolomide and concomitant radiotherapy Receives: Drug: Bevacizumab and Temozolomide and radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate according to McDonald criteria
Measured: 6 months
Secondary outcomes (1)
Progression-free survival
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2009 (estimated)
- Study startNov 2008
- Primary completionNov 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ulrik Lassen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ulrik Lassen, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817284
- Sponsor's protocol ID
- BIBT-01
- Status last verified
- Nov 2011
- First submitted
- 8 Dec 2008
- Last updated
- 30 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00817284
- Acronym / sponsor ID
- BIBT-01
- Conditions
- Glioblastoma Multiforme
- Keywords
- Newly diagnosed patients with glioblastoma multiforme., Performance status 0-2.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Ulrik LassenUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 6 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| arm I | Experimental | Drug: bevacizumab and Irinotecan and radiotherapyBevacizumab + Irinotecan and concomitant radiotherapy |
| Arm II | Experimental | Drug: Bevacizumab and Temozolomide and radiotherapyBevacizumab and Temozolomide and concomitant radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | arm I |
| Bevacizumab and Temozolomide and radiotherapyBevacizumab 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. | Drug | Arm II |
Primary outcome
Objective response rate according to McDonald criteria
Time frame: 6 months
1 secondary outcome
Progression-free survival
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2011.
Related trials for Glioblastoma Multiforme
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab and Irinotecan and radiotherapy and Bevacizumab and Temozolomide and radiotherapy in people with Glioblastoma Multiforme, run by Ulrik Lassen at 3 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate according to McDonald criteria (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2011.