Contact information
Type
Scientific
Primary contact
Prof D.J. Richel
ORCID ID
Contact details
Academic Medical Centre (AMC)
Department of Oncology
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 566 9111
D.J.Richel@amc.uva.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
15598
Study information
Scientific title
Bevacizumab in combination with metronomic dose temozolomide in patients with relapsed high grade gliomas
Acronym
AVATAR
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
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Condition
Relapsed glioma
Intervention
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
Drug
Phase
Not Specified
Drug names
Bevacizumab, temozolomide
Primary outcome measures
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
13/02/2007
Overall trial end date
01/02/2009
Reason abandoned
Eligibility
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
Patient
Age group
Not Specified
Gender
Both
Target number of participants
30
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
13/02/2007
Recruitment end date
01/02/2009
Locations
Countries of recruitment
Netherlands
Trial participating centre
Academic Medical Centre (AMC)
Amsterdam
1100 DD
Netherlands
Sponsor information
Organisation
Academic Medical Centre (AMC) (The Netherlands)
Sponsor details
Department of Internal Medicine
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Academic Medical Centre (AMC) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
Results - basic reporting
Publication summary