brain cancer glioma
Conditions
Interventions
Patients will be cohort-wise treated with kinase inhibitors for 2 weeks prior
to surgery, which is part of standard care.
During and at the end of the PKI treatment and during surgery venous
bloodsa
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients without a history of brain tumor 2. Initial brain MR-scan suggesting a high grade glioma, according to the interpretation of an expert neuroradiologist 3. On initial MR-scan a tumor localisation that is deemed resectable without major neurological deficits 4. Patients must have a Karnofsky Performance Score >= 70% 5. Patients must have a RTOG Neurologic Function Status of 0-2 6. Patients need to have adequate hematological, renal and hepatic function as assessed by the following laboratory requirements to be conducted within seven days prior to start study treatment: - Hemoglobin > 7.0 mmol/l - Absolute neutrophil count (ANC) >1,5 x 10*9/l - Platelet count > 100 x 10*9/l - ALT and AST 50 ml/min ;7. Patients are 18 years of older 8. Male and female patients with reproductive potential must use an approved contraceptive method during and for three months after discontinuation of study treatment 9. Patients need to give informed consent 10. Patients should be able to swallow oral medication
Exclusion criteria
Exclusion criteria: 1. Patients receiving prior chemotherapy, radiotherapy or anti-angiogenic therapy 2. Use of anti-coagulant therapy 3. Use of CYP3A4 enzyme-inducing drugs, other than dexamethasone (including Carbamazepine, Phenytoine, Phenobarbital) 4. Initial MR-scan of the brain showing tumor hemorrhage or intracerebral hemorrhage 5. Patients with progressive neurological symptoms despite dexamethasone 6. Inability to comply with protocol or study procedures 7. Pregnancy 8. Patients with uncontrolled arterial hypertension. Blood pressure must be grade 2 NCI-CTC version 4.0)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine PKI and active metabolites concentrations in tumor tissue after approximately two weeks of treatment in patients with a newly diagnosed HGG. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) To determine the correlation of PKI and active metabolites concentrations in tumor with PKI and active metabolites concentrations in plasma- and CSF after approximately two weeks of treatment. 2) To test the feasibility of determining the (phospho)proteomic profiles and kinase activity profiles in tumor tissue and CSF after two weeks of treatment. 3) To determine whether approximately two weeks of treatment with PKIs induces significant difference of the (phospho)proteomic profiles and kinase activities of tumor tissue from study patients and from patients in a control group (without PKI treatment prior to resection). | — |
Countries
Netherlands
Outcome results
None listed