Exploration of Circulating VE-cadherin in Metastatic Colorectal Adenocarcinoma Patients Treated With Bevacizumab

Colorectal Cancer Clinical Trial

— AVECC  

Official title:

Exploration of New Biologic Factors' Predictive Value , Especially Circulating VE-cadherin in Metastatic Colorectal Adenocarcinoma Patients Treated With Bevacizumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01405430
• Other study ID #: AVECC
• Secondary ID: ET2010-003
• Status: Completed
• Phase: N/A
• First received: July 26, 2011
• Last updated: June 26, 2015
• Start date: May 2010
• Est. completion date: May 2014

Study information

• Verified date: June 2015
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

It is a prospective, non-randomized, monocentric study. The purpose of the study is to assess the predictive value of VE-cadherin on the objective tumor response.

Biological factors will be correlated to clinical outcome measures.

100 patients treated with bevacizumab for a metastatic colorectal adenocarcinoma will be enrolled.

Patients will be followed every 10 weeks until progression in spite of bevacizumab or until they stop bevacizumab because of toxicity.

Bevacizumab will be administered according to investigators appreciation.

Blood samples will be collected at enrollment, at second bevacizumab's administration and every 10 weeks until progression, or until patients stop bevacizumab because of toxicity or until one year at most in case that patients still receive bevacizumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with a metastatic colorectal cancer proved histologically and treated with bevacizumab in first line.

• At least one extra-osseous, non-irradiated, measurable site (>= 10 mm with spiral CT).

• No prior radiotherapy treatment unless treatment is over for at least 4 weeks.

• Adult patients.

• PS <= 2.

• Life expectancy greater than 3 months.

• Mandatory affiliation with a healthy security insurance.

• Signed written informed consent.

Exclusion Criteria:

• Prior chemotherapy for the metastatic cancer.

• Prior bevacizumab treatment.

• Other current cancer or previous cancer detected in the last 5 years that can be linked to the current disease.

• Patient deprived of freedom.

• Pregnant or lactating women.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Adenocarcinoma
• Colorectal Cancer
• Metastasis

Intervention

Biological:
• Bevacizumab + blood samples
Bevacizumab will be administered according to investigators appreciation. Blood samples will be collected at enrollment, at second bevacizumab's administration and every 10 weeks until progression, or until patients stop bevacizumab because of toxicity or until one year at most in case that patients still receive bevacizumab.

Locations

Country	Name	City	State
France	Hôpital Privé Jean Mermoz	Lyon
France	Centre Léon Bérard	LYON Cedex 08

Sponsors (2)

Lead Sponsor	Collaborator
Centre Leon Berard	UMR-S Inserm 1036

Country where clinical trial is conducted

France, 

References & Publications (18)

Bouvier AM, Remontet L, Jougla E, Launoy G, Grosclaude P, Buémi A, Tretarre B, Velten M, Dancourt V, Menegoz F, Guizard AV, Macé Lesec'h J, Peng J, Bercelli P, Arveux P, Estève J, Faivre J. Incidence of gastrointestinal cancers in France. Gastroenterol Clin Biol. 2004 Oct;28(10 Pt 1):877-81. — View Citation

Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, Ryan PD, Garber JE, Chen H, Campos SM, Shulman LN, Harris LN, Gelman R, Winer EP. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res. 2008 Dec 1;14(23):7871-7. doi: 10.1158/1078-0432.CCR-08-0593. — View Citation

Corada M, Zanetta L, Orsenigo F, Breviario F, Lampugnani MG, Bernasconi S, Liao F, Hicklin DJ, Bohlen P, Dejana E. A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability. Blood. 2002 Aug 1;100(3):905-11. — View Citation

Gory-Fauré S, Prandini MH, Pointu H, Roullot V, Pignot-Paintrand I, Vernet M, Huber P. Role of vascular endothelial-cadherin in vascular morphogenesis. Development. 1999 May;126(10):2093-102. — View Citation

Gruenberger B, Tamandl D, Schueller J, Scheithauer W, Zielinski C, Herbst F, Gruenberger T. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008 Apr 10;26(11):1830-5. doi: 10.1200/JCO.2007.13.7679. — View Citation

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. — View Citation

Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, Batchelor TT, Sorensen AG. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol. 2009 Jun;6(6):327-38. doi: 10.1038/nrclinonc.2009.63. Review. — View Citation

Jubb AM, Hurwitz HI, Bai W, Holmgren EB, Tobin P, Guerrero AS, Kabbinavar F, Holden SN, Novotny WF, Frantz GD, Hillan KJ, Koeppen H. Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J Clin Oncol. 2006 Jan 10;24(2):217-27. Epub 2005 Dec 19. — View Citation

Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol. 2005 Jun 1;23(16):3706-12. Epub 2005 May 2. — View Citation

Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, Mass R, Perrou B, Nelson B, Novotny WF. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol. 2005 Jun 1;23(16):3697-705. Epub 2005 Feb 28. — View Citation

Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, Ashby MA, Dong W, Sugrue MM, Grothey A; Investigators of the BRiTE study. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist. 2009 Sep;14(9):862-70. doi: 10.1634/theoncologist.2009-0071. Epub 2009 Sep 2. — View Citation

Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008 Apr 20;26(12):2013-9. doi: 10.1200/JCO.2007.14.9930. Erratum in: J Clin Oncol. 2008 Jun;26(18):3110. J Clin Oncol. 2009 Feb 1;27(4):653. — View Citation

Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, Flockhart DA, Hancock B, Davidson N, Gralow J, Dickler M, Perez EA, Cobleigh M, Shenkier T, Edgerton S, Miller KD; ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008 Oct 1;26(28):4672-8. doi: 10.1200/JCO.2008.16.1612. Erratum in: J Clin Oncol. 2009 Jun 20;27(18):3070. — View Citation

Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. doi: 10.1056/NEJMoa0805019. — View Citation

Wallez Y, Cand F, Cruzalegui F, Wernstedt C, Souchelnytskyi S, Vilgrain I, Huber P. Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: identification of tyrosine 685 as the unique target site. Oncogene. 2007 Feb 15;26(7):1067-77. Epub 2006 Aug 14. — View Citation

Wallez Y, Vilgrain I, Huber P. Angiogenesis: the VE-cadherin switch. Trends Cardiovasc Med. 2006 Feb;16(2):55-9. Review. — View Citation

Weitz J, Koch M, Debus J, Höhler T, Galle PR, Büchler MW. Colorectal cancer. Lancet. 2005 Jan 8-14;365(9454):153-65. Review. — View Citation

Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004 Feb;10(2):145-7. Epub 2004 Jan 25. Erratum in: Nat Med. 2004 Jun;10(6):649. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate to treatment	A 30% response rate (complete or partial response) to treatment is expected. The response will be assessed according to RECIST criteria. This primary outcome measure is defined by the observation of at least one objective response during the treatment.; This outcome measure will be correlated to biological factors.	Up to 1 year at most	No
Secondary	Clinical benefit	The clinical benefit is based on complete response, partial response or stable disease.; This outcome measure will be correlated to biological factors.	At progression or up to 1 year at most	No
Secondary	Evaluation of progression-free survival	This outcome measure will be correlated to biological factors.	From the beginning of treatment to progression, death or last available information	No
Secondary	Evaluation of overall survival	This outcome measure will be correlated to biological factors.	From the beginning of treatment to death or last available information	No
Secondary	Evaluation of tumoral markers	Evaluation of ACE and Ca19-9	At progression with bevacizumab or up to 1 year of follow-up at most	No
Secondary	Evaluation of vascular toxicities	Assess the link between vascular toxicities and VE-cadherin rate. These toxicities will be assessed during the follow-up of patients.	Up to 1 year	No