AVAstin and Temozolomide Attacking Relapsed glioma

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 23

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main study parameters/endpoints:<br> 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.<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. Safety<br> 2. Overall survival<br> 3. Response rate<br> 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<br> 5. Levels of Circulating Endothelial Cells (CECs)<br> 6. Circulating Progenitor Cells (CPCs)<br> 7. Vascular Endothelial Growth Factor (VEGF)<br> 8. Placental Growth Factor (PlGF) in peripheral blood will be determined at different time points<br>

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