Back to resultsHGG-TCP (High Grade Glioma - Tumor Concentrations of Protein Kinase Inhibitors)
Primary Purpose
Cancer, High-grade Glioma
Status
Unknown status
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Sunitinib
vandetanib
Erlotinib
Sponsored by
About this trial
This is an interventional diagnostic trial for Cancer
Eligibility Criteria
Inclusion Criteria:
- Patients without a history of brain tumor
- Initial brain MR-scan suggesting a high grade glioma, according to the interpretation of an expert neuroradiologist
- On initial MR-scan a tumor localisation that is deemed resectable without major neurological deficits
- Patients must have a Karnofsky Performance Score ≥ 70%
- Patients must have a RTOG Neurologic Function Status of 0-2
- 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
- Patients are 18 years of older
- Male and female patients with reproductive potential must use an approved contraceptive method during and for three months after discontinuation of study treatment
- Patients need to give informed consent
- Patients should be able to swallow oral medication
Exclusion Criteria:
- Patients receiving prior chemotherapy, radiotherapy or anti-angiogenic therapy
- Use of anti-coagulant therapy
- Use of CYP3A4 enzyme-inducing drugs, other than dexamethasone (including Carbamazepine, Phenytoine, Phenobarbital)
- Initial MR-scan of the brain showing tumor hemorrhage or intracerebral hemorrhage
- Patients with progressive neurological symptoms despite dexamethasone
- Inability to comply with protocol or study procedures
- Pregnancy
- Patients with uncontrolled arterial hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen.
- Patients with a history of cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- Patients with evidence or history of bleeding diathesis
- Patients with a history of venous or arterial thrombo-embolic events or hemorrhagic disease during the past six months
- Patients with a history of congestive heart failure (NYHA III, IV)
- Patients with a history of peripheral vascular disease (Fontaine stage III and IV)
- Patients with stroke or myocardial infarction during the past six months
- Patients with a history of a recent peptic ulcer disease (endoscopically-proven gastric ulcer, duodenal ulcer of esophageal ulcer) during the past six months
- Patients with uncontrolled infections (> grade 2 NCI-CTC version 4.0)
Sites / Locations
- VU University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
sunitinib
vandetanib
Erlotinib
Arm Description
Outcomes
Primary Outcome Measures
PKI and active metabolites concentrations in tumor tissue
PKI concentrations and active metabolites in tumor tissue after approximately two weeks of PKI treatment will be determined.
Secondary Outcome Measures
Correlation of PKI and active metabolites concentrations in tumor.
Venous blood sampling will be performed to determine plasma drug and active metabolites concentrations after approximately one and two weeks of PKI treatment and during surgery. CSF samples will be drawn during surgery. Plasma- and CSF drug concentrations will be correlated to tumor drug concentrations. Plasma samples for pharmacodynamics will be simultaneously drawn with the on- and after treatment hematology and chemistry analysis.
Feasibility of determining the (phospho)proteomic profiles and kinase activity profiles in tumor tissue and CSF.
Kinome wide and quantitative (phospho)proteomic profiles will be determined in tumor tissue of study patients and in tumor tissue of matched controled patients. We anticipate that these profiles will reveal information on the effect of treatment on kinase abundances, phosphopeptide levels and on phosphorylation sites. Differences in levels of phosphopeptides and fold-change of phosphorylation sites will be quantified. In an exploratory design, we will determine whether observed profile differences can be correlated to drug concentrations in tumor tissue. Kinase inhibition profiles will be measured according to standard methods as developed and modified in our laboratory.
Significant difference of the (phospho)proteomic profiles and kinase activities of tumor tissue in study patients and control group.
The (phospho)proteomic profiles and kinase activity profiles will be determined in tumor tissue of study patients and in tumor tissue of patients in a control group.
Kinase inhibition profiles will be measured according to standard methods as developed and modified in our laboratory.
Full Information
NCT ID
NCT02239952
First Posted
August 28, 2014
Last Updated
October 6, 2020
Sponsor
Amsterdam UMC, location VUmc
1. Study Identification
Unique Protocol Identification Number
NCT02239952
Brief Title
HGG-TCP (High Grade Glioma - Tumor Concentrations of Protein Kinase Inhibitors)
Official Title
Pilot Study on the Determination of Tumor Concentrations of Protein Kinase Inhibitors in Patients With Newly Diagnosed High-grade Glioma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 2014 (undefined)
Primary Completion Date
November 2021 (Anticipated)
Study Completion Date
November 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine intratumoral concentration of kinase inhibitors upon 2 weeks of treatment in tumor tissue (in the brain) of patients with high-grade gliomas (HGG).
Detailed Description
In clinical trials for HGG, multiple agents targeting various oncogenic signaling pathways that play an important role in the biology of HGG have been studied, but unfortunately only a small number of patients seem to benefit from these treatment strategies. Whether these disappointing results are due to a restricted drug delivery through the blood-brain barrier, or due to differential biological characteristics of these HGGs, remains unknown. To better understand these clinical observations and to find potential insight how to overcome them, we intend to measure tumor concentrations of PKIs after approximately two weeks treatment and to determine whether these tumor concentrations correlate with plasma- and CSF concentrations of PKIs. Subsequently, we intend to determine the (phospho)proteomic profiles and kinase inhibitory activity in tumor tissue from these HGG patients after approximately two weeks of treatment with a PKI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, High-grade Glioma
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
sunitinib
Arm Type
Experimental
Arm Title
vandetanib
Arm Type
Experimental
Arm Title
Erlotinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Sunitinib
Intervention Description
50 mg once daily, oral use for 14 days
Intervention Type
Drug
Intervention Name(s)
vandetanib
Intervention Description
300 mg, once daily, oral use for 14 days
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
150 mg, once daily, oral use for 14 days
Primary Outcome Measure Information:
Title
PKI and active metabolites concentrations in tumor tissue
Description
PKI concentrations and active metabolites in tumor tissue after approximately two weeks of PKI treatment will be determined.
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Correlation of PKI and active metabolites concentrations in tumor.
Description
Venous blood sampling will be performed to determine plasma drug and active metabolites concentrations after approximately one and two weeks of PKI treatment and during surgery. CSF samples will be drawn during surgery. Plasma- and CSF drug concentrations will be correlated to tumor drug concentrations. Plasma samples for pharmacodynamics will be simultaneously drawn with the on- and after treatment hematology and chemistry analysis.
Time Frame
2 weeks
Title
Feasibility of determining the (phospho)proteomic profiles and kinase activity profiles in tumor tissue and CSF.
Description
Kinome wide and quantitative (phospho)proteomic profiles will be determined in tumor tissue of study patients and in tumor tissue of matched controled patients. We anticipate that these profiles will reveal information on the effect of treatment on kinase abundances, phosphopeptide levels and on phosphorylation sites. Differences in levels of phosphopeptides and fold-change of phosphorylation sites will be quantified. In an exploratory design, we will determine whether observed profile differences can be correlated to drug concentrations in tumor tissue. Kinase inhibition profiles will be measured according to standard methods as developed and modified in our laboratory.
Time Frame
2 weeks
Title
Significant difference of the (phospho)proteomic profiles and kinase activities of tumor tissue in study patients and control group.
Description
The (phospho)proteomic profiles and kinase activity profiles will be determined in tumor tissue of study patients and in tumor tissue of patients in a control group.
Kinase inhibition profiles will be measured according to standard methods as developed and modified in our laboratory.
Time Frame
2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients without a history of brain tumor
Initial brain MR-scan suggesting a high grade glioma, according to the interpretation of an expert neuroradiologist
On initial MR-scan a tumor localisation that is deemed resectable without major neurological deficits
Patients must have a Karnofsky Performance Score ≥ 70%
Patients must have a RTOG Neurologic Function Status of 0-2
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
Patients are 18 years of older
Male and female patients with reproductive potential must use an approved contraceptive method during and for three months after discontinuation of study treatment
Patients need to give informed consent
Patients should be able to swallow oral medication
Exclusion Criteria:
Patients receiving prior chemotherapy, radiotherapy or anti-angiogenic therapy
Use of anti-coagulant therapy
Use of CYP3A4 enzyme-inducing drugs, other than dexamethasone (including Carbamazepine, Phenytoine, Phenobarbital)
Initial MR-scan of the brain showing tumor hemorrhage or intracerebral hemorrhage
Patients with progressive neurological symptoms despite dexamethasone
Inability to comply with protocol or study procedures
Pregnancy
Patients with uncontrolled arterial hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen.
Patients with a history of cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
Patients with evidence or history of bleeding diathesis
Patients with a history of venous or arterial thrombo-embolic events or hemorrhagic disease during the past six months
Patients with a history of congestive heart failure (NYHA III, IV)
Patients with a history of peripheral vascular disease (Fontaine stage III and IV)
Patients with stroke or myocardial infarction during the past six months
Patients with a history of a recent peptic ulcer disease (endoscopically-proven gastric ulcer, duodenal ulcer of esophageal ulcer) during the past six months
Patients with uncontrolled infections (> grade 2 NCI-CTC version 4.0)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
M.E. Van Linde, MD
Phone
+31 (0)20 4444321
Email
dm-onc@vumc.nl
Facility Information:
Facility Name
VU University Medical Center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1081 HV
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M.E. Van Linde, MD
Phone
+31 (0)20 4444321
Email
dm-onc@vumc.nl
12. IPD Sharing Statement
Citations:
PubMed Identifier
35165100
Citation
van Linde ME, Labots M, Brahm CG, Hovinga KE, De Witt Hamer PC, Honeywell RJ, de Goeij-de Haas R, Henneman AA, Knol JC, Peters GJ, Dekker H, Piersma SR, Pham TV, Vandertop WP, Jimenez CR, Verheul HMW. Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma. Clin Cancer Res. 2022 Apr 14;28(8):1595-1602. doi: 10.1158/1078-0432.CCR-21-1933.
Results Reference
derived
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HGG-TCP (High Grade Glioma - Tumor Concentrations of Protein Kinase Inhibitors)
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