Pilot study on the determination of tumor concentrations of protein kinase inhibitors in patients with newly diagnosed high-grade glioma
- Conditions
- brain cancerglioma10029211
- Registration Number
- NL-OMON47042
- Lead Sponsor
- Vrije Universiteit Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
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< 2.5 x ULN
- Alkaline phosphatase < 4 x ULN
- Serum creatinine eGFR > 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
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 <=160/95 mmHg at the time of screening on a stable antihypertensive regimen.
9. Patients with a history of cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
10. Patients with evidence or history of bleeding diathesis
11. Patients with a history of venous or arterial thrombo-embolic events or hemorrhagic disease during the past six months
12. Patients with a history of congestive heart failure (NYHA III, IV)
13. Patients with a history of peripheral vascular disease (Fontaine stage III and IV)
14. Patients with stroke or myocardial infarction during the past six months
15. Patients with a history of a recent peptic ulcer disease (endoscopically-proven gastric ulcer, duodenal ulcer of esophageal ulcer) during the past six months
16. Patients with uncontrolled infections (> grade 2 NCI-CTC version 4.0)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To determine PKI and active metabolites concentrations in tumor tissue after<br /><br>approximately two weeks of treatment in patients with a newly diagnosed HGG. </p><br>
- Secondary Outcome Measures
Name Time Method <p>1) To determine the correlation of PKI and active metabolites concentrations in<br /><br>tumor with PKI and active metabolites concentrations in plasma- and CSF after<br /><br>approximately two weeks of treatment.<br /><br>2) To test the feasibility of determining the (phospho)proteomic profiles and<br /><br>kinase activity profiles in tumor tissue and CSF after two weeks of treatment.<br /><br>3) To determine whether approximately two weeks of treatment with PKIs induces<br /><br>significant difference of the (phospho)proteomic profiles and kinase activities<br /><br>of tumor tissue from study patients and from patients in a control group<br /><br>(without PKI treatment prior to resection).</p><br>