ISRCTN ISRCTN23008679
DOI https://doi.org/10.1186/ISRCTN23008679
Secondary identifying numbers 15598
Submission date
16/07/2007
Registration date
16/07/2007
Last edited
10/06/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof D.J. Richel
Scientific

Academic Medical Centre (AMC)
Department of Oncology
P.O. Box 22660
Amsterdam
1100 DD
Netherlands

Phone +31 (0)20 566 9111
Email D.J.Richel@amc.uva.nl

Study information

Study designNon-randomised, controlled, parallel group trial
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)Not specified
Study typeNot Specified
Scientific titleBevacizumab in combination with metronomic dose temozolomide in patients with relapsed high grade gliomas
Study acronymAVATAR
Study objectivesThe 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(s)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).
Health condition(s) or problem(s) studiedRelapsed glioma
InterventionThe 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Bevacizumab, temozolomide
Primary outcome measureMain 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 measures1. 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 study start date13/02/2007
Completion date01/02/2009

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexBoth
Target number of participants30
Total final enrolment23
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment13/02/2007
Date of final enrolment01/02/2009

Locations

Countries of recruitment

  • Netherlands

Study participating centre

Academic Medical Centre (AMC)
Amsterdam
1100 DD
Netherlands

Sponsor information

Academic Medical Centre (AMC) (The Netherlands)
Hospital/treatment centre

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

Website http://www.amc.uva.nl
ROR logo "ROR" https://ror.org/03t4gr691

Funders

Funder type

Hospital/treatment centre

Academisch Medisch Centrum
Private sector organisation / Universities (academic only)
Alternative name(s)
Academic Medical Center, AMC
Location
Netherlands

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article 01/08/2010 10/06/2021 Yes No

Editorial Notes

10/06/2021: Publication reference and total final enrolment added.