CancerNCT02239952
HGG-TCP (High Grade Glioma - Tumor Concentrations of Protein Kinase Inhibitors)
A study testing Sunitinib, vandetanib and Erlotinib in people with Cancer and High-grade Glioma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, High-grade Glioma
- What is being tested?
- Sunitinib, vandetanib and Erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2014to Nov 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
VU University Medical Center
Amsterdam, North Holland, 1081 HV
M.E. Van Linde, MD, +31 (0)20 4444321, dm-onc@vumc.nl
About this study
Official title: Pilot Study on the Determination of Tumor Concentrations of Protein Kinase Inhibitors in Patients With Newly Diagnosed High-grade Glioma
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).
Read the 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.
- Conditions
- Cancer, High-grade Glioma
- Medical subject headings
- Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
50 mg once daily, oral use for 14 days
vandetanibDrug
300 mg, once daily, oral use for 14 days
ErlotinibDrug
150 mg, once daily, oral use for 14 days
| Study group | Role | What they receive |
|---|---|---|
| sunitinib | Experimental | Not described Receives: Drug: Sunitinib |
| vandetanib | Experimental | Not described Receives: Drug: vandetanib |
| Erlotinib | Experimental | Not described Receives: Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 weeks
Secondary outcomes (3)
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.
Measured: 2 weeks
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.
Measured: 2 weeks
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.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2014 (estimated)
- Study startNov 2014
- Primary completionNov 2021 (estimated)
- Study completionNov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M.E. van Linde, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02239952
- Sponsor's protocol ID
- 2013.465
- Status last verified
- Oct 2020
- First submitted
- 28 Aug 2014
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 35165100
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study on the Determination of Tumor Concentrations of Protein Kinase Inhibitors in Patients With Newly Diagnosed High-grade Glioma
- ClinicalTrials.gov ID
- NCT02239952
- Acronym / sponsor ID
- 2013.465
- Conditions
- Cancer, High-grade Glioma
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Nov 2021 (estimated)
- Study completion
- Nov 2021 (estimated)
- First posted
- 15 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| sunitinib | Experimental | Drug: Sunitinib |
| vandetanib | Experimental | Drug: vandetanib |
| Erlotinib | Experimental | Drug: Erlotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sunitinib50 mg once daily, oral use for 14 days | Drug | sunitinib |
| vandetanib300 mg, once daily, oral use for 14 days | Drug | vandetanib |
| Erlotinib150 mg, once daily, oral use for 14 days | Drug | Erlotinib |
Primary outcome
PKI and active metabolites concentrations in tumor tissue
Time frame: 2 weeks
PKI concentrations and active metabolites in tumor tissue after approximately two weeks of PKI treatment will be determined.
3 secondary outcomes
Correlation of PKI and active metabolites concentrations in tumor.
Time frame: 2 weeks
Feasibility of determining the (phospho)proteomic profiles and kinase activity profiles in tumor tissue and CSF.
Time frame: 2 weeks
Significant difference of the (phospho)proteomic profiles and kinase activities of tumor tissue in study patients and control group.
Time frame: 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Derived from this study: PubMed 35165100van 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.
Related trials for Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sunitinib, vandetanib and Erlotinib in people with Cancer and High-grade Glioma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact M.E. Van Linde, MD (+31 (0)20 4444321, dm-onc@vumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PKI and active metabolites concentrations in tumor tissue (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02239952, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.