Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof D.J. Richel


Contact details

Academic Medical Centre (AMC)
Department of Oncology
P.O. Box 22660
1100 DD
+31 (0)20 566 9111

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Bevacizumab in combination with metronomic dose temozolomide in patients with relapsed high grade gliomas



Study hypothesis

The change of chemotherapeutic temozolomide schedule from conventional to metronomic treatment may overcome temozolomide resistance in patients with recurrent glioma without any major toxicity. Administration of angiogenesis inhibitor bevacizumab leads to normalisation of glioma tumour blood vessels, during a period of at least 28 days. During this normalisation window, administration of a
combination therapy is thought to be most effective. Therefore we combine bevacizumab with metronomic dose temozolomide treatment. The PFS6 (Progression Free Survival at 6 months) is about 9% in this patient group under the old treatment regimen. We expect a PFS6 of about 30% with the combination of bevacizumab and temozolomide. Therapy regimen will continue after six months.

Ethics approval

Local medical ethics committee (Medisch Ethische Commissie Academisch Medisch Centrum Amsterdam) gave approval on the 28th March 2007 (ref: MEC 07/052 # 07.17.0453).

Study design

Non-randomised, controlled, parallel group trial

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting

Not specified

Trial type

Not Specified

Patient information sheet


Relapsed glioma


The effects of the combination of Bevacizumab (10 mg every three weeks, intravenously [iv]) with daily Temozolomide (50 mg/m^2, orally) will be compared with historical data of a matched patient group. The MRI effects of (co-) administration of dexamethasone (daily 3 dd 4 mg, orally) will be examined during the first 20 days of the experiment.

Intervention type



Not Specified

Drug names

Bevacizumab, temozolomide

Primary outcome measure

Main study parameters/endpoints:
The Progression Free Survival at 6 months (PFS6) is the main study parameter. This is about 9% in this patient group under the old treatment regimen. We expect a PFS6 of about 30% with the combination of bevacizumab and temozolomide. Therapy regimen will continue after six months.

Secondary outcome measures

1. Safety
2. Overall survival
3. Response rate
4. Changes in tumour blood flow and vascular permeability (vascular permeability [Ktrans] and relative Cerebral Blood Volume [rCBV] values) during the first 20 days of treatment with bevacizumab in comparison with dexamethasone and the combination bevacizumab and dexamethasone
5. Levels of Circulating Endothelial Cells (CECs)
6. Circulating Progenitor Cells (CPCs)
7. Vascular Endothelial Growth Factor (VEGF)
8. Placental Growth Factor (PlGF) in peripheral blood will be determined at different time points

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Patients present with histologically confirmed diagnosis of intracranial recurrent high grade glial tumour (World Health Organisation [WHO] grade IV). Patients may be entered based on local pathology from the original tumour specimen
2. Patients must have evidence of tumour progression following radiation and chemotherapy as measured by Magnetic Resonance Imaging (MRI) (MRI-0 at presentation)
3. Patients may have received up to two prior chemotherapy regimens (with concurrent radiotherapy)
4. Patients may have undergone prior surgical resection and will be eligible if recovered from the effects of surgery
5. Patients must have adequate organ function, including the following:
5.1. Adequate bone marrow reserve: Absolute Neutrophil Count (ANC) greater than 1.5 x 10^9/L, platelet count greater than 100 x 10^9/L, and haemoglobin greater than g/dL (6.21 mmol/L)
5.2. Hepatic: total bilirubin less than two times the Upper Limit of Normal (ULN); Alkaline Phosphatase (ALP), Aspartate Transaminase (AST), and Alanine Transaminase (ALT) less than 3 x ULN
5.3. Renal: serum creatinine less than 1.5 ULN
These tests must be performed less than five days prior to enrolment. Eligibility for haemoglobin count may be reached by transfusion
6. Patients must have a Karnofsky Performance Score greater than 70%
7. Patients must be greater than 18 years of age, with a life expectancy of greater than eight weeks
8. Patient compliance and geographic proximity that allow for adequate follow up is required
9. Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate (for example, Intrauterine Device [IUD], birth control pills, or barrier device) during and for three months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test less than three days prior to study enrolment
10. Signed informed consent from the patient or legal representative is required

Participant type


Age group

Not Specified



Target number of participants


Participant exclusion criteria

1. Patients with inability to comply with protocol or study procedures (for example, an inability to swallow tablets)
2. Patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
3. Patients receiving EIAEDs (Enzyme-Inducing Anti-Epileptic Drugs). Patients must discontinue EIAEDs greater than 14 days prior to study enrolment. The investigator may prescribe non-EIAEDs
4. Patients receiving any other anticancer therapy, any anticoagulant therapy
5. Patients with serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram indicative of cardiac disease) that, in opinion of the investigator, would compromise the safety of the patient and his/her ability to complete the study
6. Patients with prior thrombo-embolic events

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Academic Medical Centre (AMC)
1100 DD

Sponsor information


Academic Medical Centre (AMC) (The Netherlands)

Sponsor details

Department of Internal Medicine
P.O. Box 22660
1100 DD

Sponsor type

Hospital/treatment centre



Funder type

Hospital/treatment centre

Funder name

Academic Medical Centre (AMC) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes