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

NCT01227213 | Completed

• 1 other identifier: SUMAVA
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypertension; Renal Function; Insulin Sensitivity; Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Endothelial function

  Group A: Vasomotor response to intra-arterially administered doses of acetylcholine and nitroprusside before and after start sunitinib

  2 weeks

• Insulin sensitivity

  Group B: Insulin sensitivity measured by hyperinsulinemic euglycemic clamp before and after start sunitinib

  2 weeks

• 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

Secondary Outcomes (3)

• Blood pressure

  3 months

• Weight

  3 months

• Laboratory evaluations

  12 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

30 patients with metastatic renal cell carcinoma starting treatment with sunitinib

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, 6500HB, Netherlands

Location

Related Publications (2)

• 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: 10.1097/HJH.0000000000000662.

  PMID: 26203967 RESULT

• 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. 2016 Apr;81(4):768-72. doi: 10.1111/bcp.12797. Epub 2016 Jan 14.

  PMID: 26447463 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Hypertension; Insulin Resistance; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. Rongen

Study Record Dates

• First Submitted: October 22, 2010
• First Posted: October 25, 2010
• Study Start: November 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: October 30, 2015

Record last verified: 2015-10

Locations

NL (1)