Angiogenesis Inhibitors and Hypertension: Clinical Aspects

NCT ID: NCT00511511

Last Updated: 2010-01-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-08-31

Study Completion Date

2009-12-31

Brief Summary

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The aim of the study is to find simple clinical and laboratory parameters to predict the development of hypertension and to elucidate the mechanism of hypertension during treatment with the tyrosine kinase inhibitor Sunitinib.

Detailed Description

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Inhibition of angiogenesis with antibodies against vascular endothelial growth factor (VEGF) and VEGF receptor antagonists has become an established treatment for cancer. An unanticipated side effect of angiogenesis inhibitors is the development of hypertension. The pathogenesis of this hypertension is unknown. Not all patients will develop hypertension. However, it is not known which patient will and which patient will not develop hypertension.

Conditions

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Hypertension

Study Design

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Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* Men and women, with either renal cell carcinoma or gastro intestinal stromal tumors (GIST) intended to be treated solely with Sunitinib (single-agent treatment) and who are considered fit enough by their treating physician to receive Sunitinib.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Erasmus Medical Center

OTHER

Sponsor Role lead

Principal Investigators

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A. H. van den Meiracker, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

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Erasmus MC

Rotterdam, , Netherlands

Site Status

Countries

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Netherlands

References

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Zakarija A, Soff G. Update on angiogenesis inhibitors. Curr Opin Oncol. 2005 Nov;17(6):578-83. doi: 10.1097/01.cco.0000183672.15133.ab.

Reference Type BACKGROUND
PMID: 16224236 (View on PubMed)

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.

Reference Type BACKGROUND
PMID: 15175435 (View on PubMed)

Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. doi: 10.1200/JCO.2005.05.098.

Reference Type BACKGROUND
PMID: 15681523 (View on PubMed)

Sica DA. Angiogenesis inhibitors and hypertension: an emerging issue. J Clin Oncol. 2006 Mar 20;24(9):1329-31. doi: 10.1200/JCO.2005.04.5740. Epub 2006 Jan 30. No abstract available.

Reference Type BACKGROUND
PMID: 16446321 (View on PubMed)

Veronese ML, Mosenkis A, Flaherty KT, Gallagher M, Stevenson JP, Townsend RR, O'Dwyer PJ. Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol. 2006 Mar 20;24(9):1363-9. doi: 10.1200/JCO.2005.02.0503. Epub 2006 Jan 30.

Reference Type BACKGROUND
PMID: 16446323 (View on PubMed)

Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007 Mar 13;115(10):1285-95. doi: 10.1161/CIRCULATIONAHA.106.652859. No abstract available.

Reference Type BACKGROUND
PMID: 17353456 (View on PubMed)

Kuenen BC, Levi M, Meijers JC, Kakkar AK, van Hinsbergh VW, Kostense PJ, Pinedo HM, Hoekman K. Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arterioscler Thromb Vasc Biol. 2002 Sep 1;22(9):1500-5. doi: 10.1161/01.atv.0000030186.66672.36.

Reference Type BACKGROUND
PMID: 12231573 (View on PubMed)

Bosnjak JJ, Terata K, Miura H, Sato A, Nicolosi AC, McDonald M, Manthei SA, Saito T, Hatoum OA, Gutterman DD. Mechanism of thrombin-induced vasodilation in human coronary arterioles. Am J Physiol Heart Circ Physiol. 2003 Apr;284(4):H1080-6. doi: 10.1152/ajpheart.00465.2002. Epub 2002 Dec 19.

Reference Type BACKGROUND
PMID: 12595282 (View on PubMed)

Touyz RM. Regulation of endothelial nitric oxide synthase by thrombin. Hypertension. 2007 Mar;49(3):429-31. doi: 10.1161/01.HYP.0000255955.75119.1a. Epub 2007 Jan 8. No abstract available.

Reference Type BACKGROUND
PMID: 17210837 (View on PubMed)

Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003 Jun;9(6):669-76. doi: 10.1038/nm0603-669.

Reference Type BACKGROUND
PMID: 12778165 (View on PubMed)

Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, Shah PK, Willerson JT, Benza RL, Berman DS, Gibson CM, Bajamonde A, Rundle AC, Fine J, McCluskey ER; VIVA Investigators. The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation. 2003 Mar 18;107(10):1359-65. doi: 10.1161/01.cir.0000061911.47710.8a.

Reference Type BACKGROUND
PMID: 12642354 (View on PubMed)

Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol. 1998 Mar;274(3):H1054-8. doi: 10.1152/ajpheart.1998.274.3.H1054.

Reference Type BACKGROUND
PMID: 9530221 (View on PubMed)

Li B, Ogasawara AK, Yang R, Wei W, He GW, Zioncheck TF, Bunting S, de Vos AM, Jin H. KDR (VEGF receptor 2) is the major mediator for the hypotensive effect of VEGF. Hypertension. 2002 Jun;39(6):1095-100. doi: 10.1161/01.hyp.0000018588.56950.7a.

Reference Type BACKGROUND
PMID: 12052848 (View on PubMed)

Broere A, Van Den Meiracker AH, Boomsma F, Derkx FH, Veld AJ, Schalekamp MA. Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME. Am J Physiol. 1998 Dec;275(6):F870-7. doi: 10.1152/ajprenal.1998.275.6.F870.

Reference Type BACKGROUND
PMID: 9843903 (View on PubMed)

van der Linde NA, Boomsma F, van den Meiracker AH. Role of nitric oxide in modulating systemic pressor responses to different vasoconstrictors in man. J Hypertens. 2005 May;23(5):1009-15. doi: 10.1097/01.hjh.0000166842.65097.b1.

Reference Type BACKGROUND
PMID: 15834287 (View on PubMed)

Kappers 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.

Reference Type DERIVED
PMID: 20733093 (View on PubMed)

Other Identifiers

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EudraCT-number: 2007-002038-13

Identifier Type: -

Identifier Source: secondary_id

MEC-2007-155

Identifier Type: -

Identifier Source: org_study_id

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