Chemokines and Renal Cancer - Full Text View

Purpose

Despite novel treatment options, Renal Cell Carcinoma (RCC) has been characterized by a constant increase in its mortality and consequently requires an important involvement in translational research.

The aim of this study is to evaluate the interest of CXCL4, CXCL4L1 and CXCR3 as biomarkers in localized, locally advanced or metastatic RCC. Indeed these chemokines have shown anti-angiogenic and anti-tumor properties in experimental models and may be particularly interesting for prognostic and predictive purposes.

Condition	Intervention
Carcinoma Carcinoma Renal Cell Kidney Neoplasms Kidney Diseases Chemokines	Biological: Biological sample

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Level of Expression and Prognostic Value of CXCL4, CXCL4L1 and CXCR3 in Renal Cell Carcinoma.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Kidney Cancer

U.S. FDA Resources

Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:

Prognostic value of the markers of interest (CXCL4, CXCL4L1 et CXCR3) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Prognostic value of the markers of interest (CXCL4, CXCL4L1 et CXCR3) will be evaluated by the association of these markers with time to event occurrence.

Localized or locally advanced renal cell carcinoma group:
- local recurrence
- contralateral recurrence
- extra-renal distant recurrence (metastatic progression)
- specific cancer death
- nonspecific cancer death
Metastatic renal cell carcinoma group :
- local recurrence for patients who underwent a nephrectomy
- contralateral reccurence
- metastatic progression
- specific cancer death
- nonspecific cancer death

Secondary Outcome Measures:

Predictive value of therapeutic response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Predictive value of therapeutic response will be assessed for patients receiving systemic therapy. It will be evaluated by the association of markers of interest with the therapeutic response.
- RECIST criteria: patients showing a complete response or a partial response, will be considered as "responders"
- The progression of the longest diameter of tumor, the proportion of intra-tumor necrosis (Choi criteria) and +/- the perfusion characteristics of tumor if primitive tumor

Biospecimen Retention: Samples With DNA

whole blood, urine and tissues

Estimated Enrollment:	310
Study Start Date:	June 2011
Estimated Study Completion Date:	June 2019
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Group A. Surgically treated patients Patients having a radical or partial nephrectomy.	Biological: Biological sample 2 blood samples of 10mL + one urine sample on pre-operative d-1/d, post-operative d1 and d5(+/-2), one month post-operative, at the end of the study in the absence of disease progression or at the date of recurrence or progression if the case arises.
Group B. Patients treated with targeted therapies Patients treated by RCC-directed targeted therapy	Biological: Biological sample 2 blood samples of 10mL + one urine sample before starting the therapy at first therapeutic evaluation (2 or 3 months depending on the treatment chosen) at the end of the study or at the date of disease progression.

Detailed Description:

Based on a physiopathological rationale, the use of RCC-directed antiangiogenic therapies into clinical practice leads to conclusive results and makes RCC a particularly well-suited tumor type to study factors involved in the angiogenic process. Furthermore the intensive use of targeted therapies in clinical practice raised new questions about their management.

Therefore the identification of new molecular biomarkers is important:

to improve the precision of prognostic models currently based on clinical, biological or histopathological variables
to identify high risk patients that could benefit from an adjuvant treatment or a closer postoperative follow-up
to predict the response to antiangiogenic therapies and therefore identify the drug which is likely to be the most effective within an ever increasing pharmacopeia
to follow the therapy as precisely as possible, predict or attest the disease progression justifying a therapeutic modification

Low CXCL4, CXCL4L1 and CXCR3 tumor expression levels are associated with bad prognosis factors in RCC. Consequently their interest in RCC is worth being evaluated, in two subgroups : Localized / locally advanced renal cell carcinoma and Metastatic renal cell carcinoma.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients diagnosed with localized, locally advanced or metastatic Renal Cell Carcinoma

Criteria

Inclusion Criteria:

Patients diagnosed with localized, locally advanced or metastatic Renal Cell Carcinoma :
- having a radical or partial nephrectomy
- or treated by RCC-directed targeted therapy
Patients who have signed and dated an informed consent form with the investigator

Exclusion Criteria:

under 18 years old

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01339975

Contacts

Contact: Alain RAVAUD, Pr

(33) 05.56.79.58.08

alain.ravaud@chu-bordeaux.fr

Locations

France
University Bordeaux Hospital	Recruiting
Bordeaux, France, 33076
Contact: Jean-Christophe BERNHARD, Dr jean-christophe.bernhard@chu-bordeaux.fr
Principal Investigator: Jean-Christophe BERNHARD, Dr

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

Principal Investigator:	Jean-Christophe BERNHARD, Dr	University Hospital Bordeaux, France
Study Chair:	Adélaïde DOUSSAU, Dr	Bordeaux University Hospital

More Information

Publications:

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Margulis V, Sánchez-Ortiz RF, Tamboli P, Cohen DD, Swanson DA, Wood CG. Renal cell carcinoma clinically involving adjacent organs: experience with aggressive surgical management. Cancer. 2007 May 15;109(10):2025-30.

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Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24.

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34.

Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11.

Ravaud A, Wallerand H, Culine S, Bernhard JC, Fergelot P, Bensalah K, Patard JJ. Update on the medical treatment of metastatic renal cell carcinoma. Eur Urol. 2008 Aug;54(2):315-25. Epub 2008 May 5. Review.

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Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003 Jun 2;197(11):1537-49.

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Struyf S, Burdick MD, Proost P, Van Damme J, Strieter RM. Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. Circ Res. 2004 Oct 29;95(9):855-7. Epub 2004 Sep 30.

Struyf S, Burdick MD, Peeters E, Van den Broeck K, Dillen C, Proost P, Van Damme J, Strieter RM. Platelet factor-4 variant chemokine CXCL4L1 inhibits melanoma and lung carcinoma growth and metastasis by preventing angiogenesis. Cancer Res. 2007 Jun 15;67(12):5940-8.

Pan J, Burdick MD, Belperio JA, Xue YY, Gerard C, Sharma S, Dubinett SM, Strieter RM. CXCR3/CXCR3 ligand biological axis impairs RENCA tumor growth by a mechanism of immunoangiostasis. J Immunol. 2006 Feb 1;176(3):1456-64.

Klatte T, Seligson DB, Leppert JT, Riggs SB, Yu H, Zomorodian N, Kabbinavar FF, Strieter RM, Belldegrun AS, Pantuck AJ. The chemokine receptor CXCR3 is an independent prognostic factor in patients with localized clear cell renal cell carcinoma. J Urol. 2008 Jan;179(1):61-6. Epub 2007 Nov 13.

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Bensalah K, Pantuck AJ, Crepel M, Verhoest G, Méjean A, Valéri A, Ficarra V, Pfister C, Ferrière JM, Soulié M, Cindolo L, De La Taille A, Tostain J, Chautard D, Schips L, Zigeuner R, Abbou CC, Lobel B, Salomon L, Lechevallier E, Descotes JL, Guillé F, Colombel M, Belldegrun AS, Patard JJ. Prognostic variables to predict cancer-related death in incidental renal tumours. BJU Int. 2008 Nov;102(10):1376-80. Epub 2008 Aug 22.

Furniss D, Harnden P, Ali N, Royston P, Eisen T, Oliver RT, Hancock BW; National Cancer Research Institute Renal Clinical Studies Group. Prognostic factors for renal cell carcinoma. Cancer Treat Rev. 2008 Aug;34(5):407-26. Epub 2008 Apr 28. Review.

Responsible Party:	University Hospital, Bordeaux
ClinicalTrials.gov Identifier:	NCT01339975 History of Changes
Other Study ID Numbers:	CHUBX 2010/45
Study First Received:	April 20, 2011
Last Updated:	January 10, 2013
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:

Kidney Neoplasms
Renal Cell Carcinoma
Nephrectomy
Antiangiogenics
Chemokines
Prognostic value
Carcinoma
Carcinoma, Renal Cell
Kidney Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urologic Diseases
Adjuvants, Immunologic
Physiological Effects of Drugs
Pharmacologic Actions
Biomarkers
Targeted therapies
Surgery

Additional relevant MeSH terms:

Kidney Neoplasms
Neoplasms
Carcinoma
Carcinoma, Renal Cell
Kidney Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma

Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urologic Diseases
Adjuvants, Immunologic
Physiological Effects of Drugs
Immunologic Factors
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013

Chemokines and Renal Cancer (ChemoRenCan)