Renal Cell Cancer MetastaticNCT04368546
Sunitinib Treatment on Tissue Sodium Accumulation (TSS2)
An observational study of Renal Cell Cancer Metastatic and Hypertension, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
Here, it is investigated how sunitinib, a tyrosine kinase-inhibitor targeting vascular endothelial growth factor receptors, might influence sodium homeostasis in the skin and if this is related to a well-described treatment side-effect of sunitinib, hypertension. Read more about this study
- Who is it for?
- Ages 18 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Renal Cell Cancer Metastatic, Hypertension, Sodium Imbalance
- What is being tested?
- Sunitinib
- How many people
- 6 participants
- Where
- 1 siteGermany
- Study dates
- 1 Nov 2015to 1 Mar 2020
- Phase
- Observational
- 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 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with metastatic renal cell carcinome in the primary care of the Charité - Universitätsmedizin Berlin as well as healthy subjects without known disease recruited in the Charité - Universitätsmedizin Berlin and healthy volunteers form the Max-Delbrück Center of Molecular Medicine
Who may be able to join
- Age men > 18 years
- Life-expectation > 3 months
- Stable weight
- Blood pressure below 140/90 mmHg at baseline
- Estimated glomerular filtration rate > 45 ml/min/1.73m2
- Willingness to give written informed consent
Who cannot join
- Heart failure
- Liver disease with ascites
- Nephrotic syndrome
- Gastrointestinal complaints, preventing normal daily food intake or diarrhea
- Any form of diabetes mellitus
- Known autoimmune diseases
- Acute or chronic infection
- Alcohol or substance abuse
Trial locations and contacts
1 site in 1 country.
Germany1 site
Experimental and Clinical Research Center, Clinical Research Unit
Berlin, 13125
About this study
Official title: Effect of Sunitinib Treatment on Tissue Sodium Accumulation in Patients With Renal Cancer: a Pilot Study
Here, it is investigated how sunitinib, a tyrosine kinase-inhibitor targeting vascular endothelial growth factor receptors, might influence sodium homeostasis in the skin and if this is related to a well-described treatment side-effect of sunitinib, hypertension.
Read the detailed description
Tyrosine kinases-inhibitors targeting vascular endothelial growth factor (VEGF)-receptors (RTKIs) are increasingly used in oncology in several metastatic tumor types. These agents are featured by toxicities including hypertension. According to a new insight, sodium in response to a high dietary sodium intake, is accumulated in a hyperosmolar way in the interstitial compartment. In response to this high sodium concentration cells of the mononuclear phagocytic system (MPS) are activated resulting in an increased production of VEGF-C, activation of VEGF type 3 receptors and formation of a lymphatic capillary network, involved in clearance of interstitial sodium. Blockade of stimulation of VEGF-C receptors or depletion of MPS cells in rodents has been associated with salt-sensitive hypertension.
Sunitinib is an orally-active, multitarget RTKI mainly used for the treatment of patients with metastatic renal cancer and imatinib-resistant gastrointestinal stromal tumors. Sunitinib blocks all three VEGF receptors subtypes, including VEGF-receptor type 3.
The investigators hypothesize that treatment of patients with sunitinib is associated with tissue sodium accumulation and this accumulation contributes to the rise in blood pressure. Tissue sodium is measured by using a newly developed 23Na magnetic resonance-imaging (MRI) technique which allows a non-invasive and contrast agent-free sodium content measurement in the muscle and skin of the lower leg.
- Conditions
- Renal Cell Cancer Metastatic, Hypertension, Sodium Imbalance
- Being tested
- Sunitinib
- Keywords
- Sunitinib, Tyrosine kinases-inhibitor, Sodium, MRI, Skin
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Diagnostic test: 23Na-MRI
| Study group | Role | What they receive |
|---|---|---|
| Patients | Metastatic cell carcinoma patients before sunitinib treatment, after 4 week on, after 2 week off and finally again 4 week on medication. Receives: Drug: Sunitinib | |
| Healthy controls | Age-matched subjects without known disease. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skin sodium
Changes in sodium content measured by 23Na magnetic resonance-imaging (MRI) technique
Measured: 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)
Secondary outcomes (1)
Plasma VEGF-C
Concentration of VEGF-C in patients plasma
Measured: 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2020
- Study start1 Nov 2015
- Primary completion1 Feb 2019
- Study completion1 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Renal Cell Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe 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
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- German Heart Institute
- Responsible party
- Principal investigator, Dr. Lajos Marko, Charite University, Berlin, Germany
- Investigators
- Dominik Müller, PhD, Study director, Group leader at the Max Delbruck Center for Molecular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04368546
- Sponsor's protocol ID
- ChariteU-ECRC-TSS2
- Other IDs
- EA1/044/15
- Status last verified
- Jan 2021
- First submitted
- 27 Apr 2020
- Last updated
- 27 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kandula P, Agarwal R. Proteinuria and hypertension with tyrosine kinase inhibitors. Kidney Int. 2011 Dec;80(12):1271-7. doi: 10.1038/ki.2011.288. Epub 2011 Sep 7.
PubMed 21900879Kappers MH, van Esch JH, Sluiter W, Sleijfer S, Danser AH, van den Meiracker AH. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension. 2010 Oct;56(4):675-81. doi: 10.1161/HYPERTENSIONAHA.109.149690. Epub 2010 Aug 23.
PubMed 20733093Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park JK, Beck FX, Muller DN, Derer W, Goss J, Ziomber A, Dietsch P, Wagner H, van Rooijen N, Kurtz A, Hilgers KF, Alitalo K, Eckardt KU, Luft FC, Kerjaschki D, Titze J. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009 May;15(5):545-52. doi: 10.1038/nm.1960. Epub 2009 May 3.
PubMed 19412173Kopp C, Linz P, Dahlmann A, Hammon M, Jantsch J, Muller DN, Schmieder RE, Cavallaro A, Eckardt KU, Uder M, Luft FC, Titze J. 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension. 2013 Mar;61(3):635-40. doi: 10.1161/HYPERTENSIONAHA.111.00566. Epub 2013 Jan 21.
PubMed 23339169
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Sunitinib Treatment on Tissue Sodium Accumulation in Patients With Renal Cancer: a Pilot Study
- ClinicalTrials.gov ID
- NCT04368546
- Acronym / sponsor ID
- ChariteU-ECRC-TSS2
- Conditions
- Renal Cell Cancer Metastatic, Hypertension, Sodium Imbalance
- Keywords
- Sunitinib, Tyrosine kinases-inhibitor, Sodium, MRI, Skin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- German Heart Institute
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 1 Feb 2019 (actual)
- Study completion
- 1 Mar 2020 (actual)
- First posted
- 29 Apr 2020 (actual)
- 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.
Here, it is investigated how sunitinib, a tyrosine kinase-inhibitor targeting vascular endothelial growth factor receptors, might influence sodium homeostasis in the skin and if this is related to a well-described treatment side-effect of sunitinib, hypertension.
Detailed description
Tyrosine kinases-inhibitors targeting vascular endothelial growth factor (VEGF)-receptors (RTKIs) are increasingly used in oncology in several metastatic tumor types. These agents are featured by toxicities including hypertension. According to a new insight, sodium in response to a high dietary sodium intake, is accumulated in a hyperosmolar way in the interstitial compartment. In response to this high sodium concentration cells of the mononuclear phagocytic system (MPS) are activated resulting in an increased production of VEGF-C, activation of VEGF type 3 receptors and formation of a lymphatic capillary network, involved in clearance of interstitial sodium. Blockade of stimulation of VEGF-C receptors or depletion of MPS cells in rodents has been associated with salt-sensitive hypertension.
Sunitinib is an orally-active, multitarget RTKI mainly used for the treatment of patients with metastatic renal cancer and imatinib-resistant gastrointestinal stromal tumors. Sunitinib blocks all three VEGF receptors subtypes, including VEGF-receptor type 3.
The investigators hypothesize that treatment of patients with sunitinib is associated with tissue sodium accumulation and this accumulation contributes to the rise in blood pressure. Tissue sodium is measured by using a newly developed 23Na magnetic resonance-imaging (MRI) technique which allows a non-invasive and contrast agent-free sodium content measurement in the muscle and skin of the lower leg.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Drug: SunitinibMetastatic cell carcinoma patients before sunitinib treatment, after 4 week on, after 2 week off and finally again 4 week on medication. |
| Healthy controls | – | –Age-matched subjects without known disease. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with metastatic renal cell carcinome in the primary care of the Charité - Universitätsmedizin Berlin as well as healthy subjects without known disease recruited in the Charité - Universitätsmedizin Berlin and healthy volunteers form the Max-Delbrück Center of Molecular Medicine
Key inclusion criteria (6 listed)
- Age men > 18 years
- Life-expectation > 3 months
- Stable weight
- Blood pressure below 140/90 mmHg at baseline
- Estimated glomerular filtration rate > 45 ml/min/1.73m2
Key exclusion criteria (8 listed)
- Heart failure
- Liver disease with ascites
- Nephrotic syndrome
- Gastrointestinal complaints, preventing normal daily food intake or diarrhea
- Any form of diabetes mellitus
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 |
|---|---|---|
| SunitinibAlso: Diagnostic test: 23Na-MRI | Drug | Patients |
Primary outcome
Skin sodium
Time frame: 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)
Changes in sodium content measured by 23Na magnetic resonance-imaging (MRI) technique
1 secondary outcome
Plasma VEGF-C
Time frame: 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Background: PubMed 21900879Kandula P, Agarwal R. Proteinuria and hypertension with tyrosine kinase inhibitors. Kidney Int. 2011 Dec;80(12):1271-7. doi: 10.1038/ki.2011.288. Epub 2011 Sep 7.
- Background: PubMed 20733093Kappers MH, van Esch JH, Sluiter W, Sleijfer S, Danser AH, van den Meiracker AH. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension. 2010 Oct;56(4):675-81. doi: 10.1161/HYPERTENSIONAHA.109.149690. Epub 2010 Aug 23.
- Background: PubMed 19412173Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park JK, Beck FX, Muller DN, Derer W, Goss J, Ziomber A, Dietsch P, Wagner H, van Rooijen N, Kurtz A, Hilgers KF, Alitalo K, Eckardt KU, Luft FC, Kerjaschki D, Titze J. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009 May;15(5):545-52. doi: 10.1038/nm.1960. Epub 2009 May 3.
- Background: PubMed 23339169Kopp C, Linz P, Dahlmann A, Hammon M, Jantsch J, Muller DN, Schmieder RE, Cavallaro A, Eckardt KU, Uder M, Luft FC, Titze J. 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension. 2013 Mar;61(3):635-40. doi: 10.1161/HYPERTENSIONAHA.111.00566. Epub 2013 Jan 21.
- Individual participant dataSharing planned: No
Related trials for Renal Cell Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1/2
Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer
Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Metastatic Melanoma, Advanced Locoregional Melanoma
Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Breast Cancer, Ovarian Cancer
RecruitingPhase 1
Open-Label Phase 1/2 Study of NEO-811 in Subjects With Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma
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.
Dominik Müller, PhD study director
Group leader at the Max Delbruck Center for Molecular Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Renal Cell Cancer Metastatic and Hypertension, run by Charite University, Berlin, Germany at 1 site in Germany.
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 6 inclusion and 8 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: finished, as of the sponsor's last update on 27 Jan 2021. 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 Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skin sodium (time frame: 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication)). 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 NCT04368546, which also lists 4 linked publications.
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 27 Jan 2021.