Bevacizumab in combination with metronomic dose temozolomide in patients with relapsed high grade gliomas - BEvacizumab + TEmozolomide in Relapsed glioma

• Conditions: Patients with a recurrent high grade glioma (after primary treatment); MedDRA version: 9.1Level: LLTClassification code 10018338Term: Glioma

• Registration Number: EUCTR2007-000488-38-NL
• Lead Sponsor: Academic Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02-20
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Patients are eligible to be included in the study if they meet all of the following criteria:
1. Patients present with histologically confirmed diagnosis of intracranial recurrent high grade glial tumor (WHO grade IV). Patients may be entered based on local pathology from the original tumor specimen.
2. Patients must have evidence of tumor progression following radiation and chemotherapy as measured by 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:
a. Adequate bone marrow reserve: Absolute neutrophil count (ANC) > 1.5 x 109/L, platelet count > 100 x 109/L, and hemoglobin > g/dL (6.21 mmol/L).
b. Hepatic: total bilirubin < 2 times the upper limit of normal (ULN); alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) < 3 x ULN.
c. Renal: Serum creatinine < 1.5 ULN.
These tests must be performed < 5 days prior to enrollment. Eligibility for hemoglobin count may be reached by transfusion.
6. Patients must have a Karnofsky Performance Score > 70%.
7. Patients must be > 18 years of age, with a life expectancy of greater than 8 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 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test < 3 days prior to study enrollment.
10. Signed informed consent from the patient or legal representative is required.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:
11. Patients with inability to comply with protocol or study procedures (for example, an inability to swallow tablets).
12. 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.
13. Patients receiving EIAEDs (Enzyme-inducing antiepileptic drugs). Patients must discontinue EIAEDs > 14 days prior to study enrollment. The investigator may prescribe non-EIAEDs.
14. Patients receiving any other anticancer therapy, any anticoagulant therapy.
15. 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.
16. Patients with prior thrombo-embolic events.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Six month progression free survival (PFS6) in patients with recurrent high grade gliomas treated with bevacizumab and metronomic dose temozolomide, compared to historical controls (PFS6 = 10%).;Secondary Objective: 1. Safety<br>2. Overall survival <br>3. Response rate<br>4. Changes in tumor blood flow and vascular permeability (Ktrans and rCBV values) during the first 20 days of treatment with bevacizumab in comparison with dexamethasone and the combination bevacizumab + dexamethasone. <br>5. Biomarkers in periferal blood;Primary end point(s): Six month progression free survival in patients with recurrent high grade gliomas treated with bevacizumab and metronomic dose temozolomide, compared to historical controls (PFS6 = 10%).