The Vascular and Metabolic Effects of Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Hypertension Clinical Trial

Official title:

The Vascular and Metabolic Effects of Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227213
• Other study ID #: SUMAVA
• Status: Completed
• Phase: N/A
• First received: October 22, 2010
• Last updated: October 29, 2015
• Start date: November 2010
• Est. completion date: November 2013

Study information

• Verified date: October 2015
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Observational

Clinical Trial Summary

Rationale: The introduction of angiogenesis inhibitors, like sunitinib and bevacizumab, has improved the outcome of patients with several types of cancer remarkably. However, their application is hampered by side effects, such as development of hypertension with consequences for renal and cardiac function. Moreover patients treated with angiogenesis inhibitors may suffer from weight loss, and insulin sensitivity during treatment appears to change. The treatment with angiogenesis inhibitors, will improve life expectancy of patients with various cancer diagnoses and therefore the clinical relevance of both short term and long lasting adverse events will translate into reduced quality of life. In addition, premature withdrawal of angiogenesis inhibitors due to side effects may result in lower response, shorter duration of response and possibly a shorter survival. Therefore, adequate treatment of above mentioned side effects in patients treated with angiogenesis inhibitors is of relevance for the response rate, the duration of progression free survival and overall survival and for quality of life.

Mechanistic insight in the pathogenesis of these side effects will help optimizing treatment.

Objective: The primary objective of the study is to investigate the effect of sunitinib on endothelial function, insulin sensitivity, renal function and renal blood flow.

Study design: Single-centre non randomized observational study Study population: 30 Patients (>18 years old) starting with sunitinib as treatment for metastatic renal cell carcinoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject is able and willing to sign the Informed Consent Form

• Age 18 years or older

• WHO performance status 0-2

• Life expectancy = 12 weeks

• mRCC patients in which the treatment of choice is sunitinib

Exclusion Criteria:

• Use of corticosteroids

• Any evidence of severe or uncontrolled diseases other than renal cell carcinoma eg, unstable or uncompensated respiratory, cardiac, hepatic or renal disease.

• Known risk of the patient transmitting HIV, hepatitis B or C via infected blood

• Patients being treated with oral anticoagulants if to be included in group A.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Hypertension
• Insulin Sensitivity
• Renal Cell Carcinoma
• Renal Function

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

Thijs AM, Tack CJ, van der Graaf WT, Rongen GA, van Herpen CM. The early effect of sunitinib on insulin clearance in patients with metastatic renal cell carcinoma. Br J Clin Pharmacol. 2015 Oct 8. doi: 10.1111/bcp.12797. [Epub ahead of print] — View Citation

Thijs AM, van Herpen CM, Verweij V, Pertijs J, van den Broek PH, van der Graaf WT, Rongen GA. Impaired endothelium-dependent vasodilation does not initiate the development of sunitinib-associated hypertension. J Hypertens. 2015 Oct;33(10):2075-82. doi: 10 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelial function	Group A: Vasomotor response to intra-arterially administered doses of acetylcholine and nitroprusside before and after start sunitinib	2 weeks	No
Primary	Insulin sensitivity	Group B: Insulin sensitivity measured by hyperinsulinemic euglycemic clamp before and after start sunitinib	2 weeks	No
Primary	GFR and renal perfusion flow	Group C: GFR and RPF measured by PAH and inulin clearance before and after start of treatment with sunitinib	2 weeks	No
Secondary	Blood pressure		3 months	No
Secondary	Weight		3 months	No
Secondary	Laboratory evaluations		12 weeks	No