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

Phase 2

Conditions: brain tumor
Recurrent high grade glial tumors
10029211

Registration Number: NL-OMON30453

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

1. Patients present with histologically confirmed diagnosis of intracranial recurrent high grade glial tumor (WHO grade IV, including gliosarcomas).
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.
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. Signed informed consent from the patient or legal representative is required.

Exclusion Criteria

9. Patients with inability to comply with protocol or study procedures (for example, an inability to swallow tablets).
10. 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.
11. Patients receiving EIAEDs (Enzyme-inducing antiepileptic drugs). Patients must discontinue EIAEDs > 14 days prior to study enrollment.
12. Patients receiving any other anticancer therapy, any anticoagulant therapy.
13. Patients with serious concomitant systemic disorders that, in opinion of the investigator, would compromise the safety of the patient and his/her ability to complete the study.
14. Patients with prior thrombo-embolic events.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The effects of the combination of Bevacizumab (10mg/kg every 3 weeks, iv) with<br /><br>daily Temozolomide (50 mg/m2, orally) will be compared with historical data of<br /><br>a matched patient group. The MRI effects of (co-) administration of<br /><br>dexamethasone (daily 3 dd 4 mg, orally) will be examined during the first 20<br /><br>days of the experiment.<br /><br>Main study parameters/endpoints: The progression free survival at 6 months<br /><br>(PFS6) is the main study parameter. This is about 9% in this patient group<br /><br>under the old treatment regimen. We expect a PFS6 of about 30% with the<br /><br>combination of bevacizumab and temozolomide. Therapy regimen will continue<br /><br>after 6 months. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Safety<br /><br>- Overall survival<br /><br>- Response rate<br /><br>- Changes in tumor blood flow and vascular permeability (Ktrans and rCBV<br /><br>values) during the first 20 days of treatment with bevacizumab in comparison<br /><br>with dexamethasone and the combination bevacizumab + dexamethasone.<br /><br>- Levels of Circulating Endothelial Cells (CECs), Circulating Progenitor Cells<br /><br>(CPCs), Vascular endothelial growth factor (VEGF), Placental growth factor<br /><br>(PlGF) and clotting factors in peripheral blood will be determined at different<br /><br>time points</p><br>