Sunitinib Treatment on Tissue Sodium Accumulation (TSS2)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Sunitinib Treatment on Tissue Sodium Accumulation in Patients With Renal Cancer: a Pilot Study

Conditions
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Renal Cell Cancer Metastatic, Hypertension, Sodium Imbalance

Intervention / Treatment
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* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>Metastatic cell carcinoma patients before sunitinib treatment, after 4 week on, after 2 week off and finally again 4 week on medication. | Drug: Sunitinib<br> <br> * Other names: Diagnostic test: 23Na-MRI;|
| Healthy controls<br>Age-matched subjects without known disease. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin sodium | Changes in sodium content measured by 23Na magnetic resonance-imaging (MRI) technique | 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma VEGF-C | Concentration of VEGF-C in patients plasma | 3 months (before, 4 weeks on, 2 weeks off and 4 weeks on medication) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sunitinib, Tyrosine kinases-inhibitor, Sodium, MRI, Skin