Primary Objective is to study the anti-tumor activity of the combination bevacizumab and metronomic dose temozolomide in patients with recurrent high grade gliomas. Secondary Objective is to investigate the effects of dexamethasone and bevacizumab…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The effects of the combination of Bevacizumab (10mg/kg every 3 weeks, iv) with
daily Temozolomide (50 mg/m2, 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.
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 6 months.
Secondary outcome
- Safety
- Overall survival
- Response rate
- 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.
- Levels of Circulating Endothelial Cells (CECs), Circulating Progenitor Cells
(CPCs), Vascular endothelial growth factor (VEGF), Placental growth factor
(PlGF) and clotting factors in peripheral blood will be determined at different
time points
Background summary
There is no standard treatment for recurrent glioma, a disease with 14%
surviving patients after 12 months. 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 normalization of
glioma tumor blood vessels, during a period of at least 28 days. During this
normalization window, administration of a combination therapy is thought to be
most effective. Therefore we combine bevacizumab with metronomic dose
temozolomide treatment. Changes of intra tumoral blood flow and permeability
due to bevacizumab administration are well visualized on MRI. During the first
20 days of the trial these changes will be compared to the effects of
dexamethasone (co-) administration on MR Imaging.
Study objective
Primary Objective is to study the anti-tumor activity of the combination
bevacizumab and metronomic dose temozolomide in patients with recurrent high
grade gliomas. Secondary Objective is to investigate the effects of
dexamethasone and bevacizumab combined with temozolomide on MRI blood flow and
permeability of tumor vasculature in patients with recurrent high grade
gliomas, during the first 20 days of the study.
Study design
The study will employ a prospective observational single centre study with
multiple time measures in 30 patients with recurrent high grade glioma.
Intervention
Not applicable.
Study burden and risks
Burden and risks associated with participation are medium. Five extra visits
are necessary for MRI scanning with contrast administration, combined with
blood sample collection. Every 3 weeks bevacizumab is administered by
intravenous infusion. Daily temozolomide is taken orally. Side effects are
monitored during the regularly scheduled outpatient clinic visits.
Postbus 22660
1100 DD Amsterdam
Nederland
Postbus 22660
1100 DD Amsterdam
Nederland
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-000488-38-NL |
| CCMO | NL15598.018.07 |