Evaluation of Contrast-Enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases - Full Text View

Purpose

Bevacizumab, an anti-angiogenic agent, plus fluorouracil based chemotherapy is considered a new standard for the treatment of metastatic colorectal cancer. Contrast-enhanced ultrasound with gas-encapsulated microbubbles can be used to assess tumour vascularity, particularly hepatic metastases, and may become a useful tool for monitoring anti-angiogenic therapies. The aim of this prospective, multicenter, non-randomized study is to evaluate the usefulness of hepatic contrast-enhanced ultrasound to predict response to bevacizumab based chemotherapy in patient with metastatic colorectal cancer. The primary objective of this study is to compare the functional vascular changes related to bevacizumab based chemotherapy and evaluated by hepatic contrast-enhanced ultrasound with classic RECIST criteria. The secondary objectives are to do a characterization of the pharmacokinetic of bevacizumab, to explore the pharmacodynamic effects of bevacizumab on functional vascular changes of hepatic metastases evaluated by hepatic contrast-enhanced ultrasound and to analyze the possible relationships between treatment efficacy or toxicity and constitutional gene polymorphisms linked to the bevacizumab.

Condition	Intervention
Metastatic Colorectal Cancer	Device: real-time contrast-enhanced ultrasound imaging (CEUS)

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Medical and Economical Evaluation of Contrast-Enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Bevacizumab

U.S. FDA Resources

Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:

functional vascular changes in tumour vascularity of hepatic metastases [ Time Frame: 2 months ] [ Designated as safety issue: No ]
Pharmacokinetic of bevacizumab between each cure of bevacizumab based chemotherapy [ Time Frame: 2 months ] [ Designated as safety issue: No ]
ratio cost/benefit of a strategy of therapeutic monitoring by contrast-enhanced ultrasound [ Time Frame: 2 months ] [ Designated as safety issue: No ]
evaluation of the response to bevacizumab based chemotherapy by RECIST criteria [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

bevacizumab-related toxicity [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
response duration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
time to disease progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
survival time [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	January 2007
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 (single arm) patient with histologically confirmed colorectal tumor treated in first line by a bevacizumab based chemotherapy	Device: real-time contrast-enhanced ultrasound imaging (CEUS) Real time contrast enhanced sonography was performed using an ultrasound dedicated system after bolus injection of 1.2 and 2x2.4 ml Sonovue ® (Bracco, Milan, Italy)

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed colorectal tumor
first line treatment by a bevacizumab based chemotherapy
Target hepatic metastases of size lower than 5 cm and higher than 5 mm detected by conventional ultrasonography and CT or MRI
Life expectancy > 2 months
OMS status =< 2
Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0
informed consent signed

Exclusion Criteria:

no target hepatic lesion detected by conventional ultrasonography
Prior bevacizumab treatment
Prior chemotherapy treatment for advanced disease
Clinically significant cardiac disease (e.g. myocardial infarction or stroke within 12 months, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure not well controlled with medication, endocarditis and prosthetic valve) and any contraindications in sulphur hexafluoride administration
Blood pressure >= 180/110 mmHg
Daily and chronic treatment by aspirin or AINS
Anticipation of need for major surgical procedure within 7 days prior day 0
Urine protein > 1g/24 Hours
Any contraindication in enhancing bevacizumab treatment
Serious, uncontrolled, concurrent infection(s) or illness(es)
pregnant and lactating woman

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489697

Contacts

Contact: François TRANQUART, Professor	33 2 47 47 38 48	tranquart@med.univ-tours.fr
Contact: Thierry LECOMTE, Doctor	33 2 47 47 47 47 ext 71730	lecomt_t@med.univ-tours.fr

Locations

France
CRLCC, Centre Paul Papin	Recruiting
Angers, France, 49033
Contact: Erick GAMELIN, Professor 33 2 41 35 27 08 e.gamelin@unimedia.fr
Contact: Virginie BERGER, Doctor 33 2 41 35 27 34 v.berger@unimedia.fr
Principal Investigator: Erick GAMELIN, Professor
Sub-Investigator: Virginie BERGER, Doctor
Sub-Investigator: Emmanuelle ANGLADE, Doctor
CHRU d'ANGERS	Recruiting
Angers, France, 49033
Contact: Christophe AUBE, Dr 33 2 41 35 36 60 chaube@chu-angers.fr
Principal Investigator: Christophe AUBE, Pr
Sub-Investigator: Jérôme LEBIGOT, Dr
Sub-Investigator: Catherine RIDEREAU ZINS, Dr
Sub-Investigator: Julien BAUDON, Dr
Sub-Investigator: Dominique LUET, Dr
CHRU Besancon	Recruiting
Besançon, France, 25000
Contact: Philippe MANZONI, Dr 33 3 81 21 81 95 rc@chu-besancon.fr
Contact: Christophe BORG, Dr 33 3 81 61 56 15 christophe.borg@efs.sante.fr
Principal Investigator: Philippe MANZONI, Dr
Sub-Investigator: Christophe BORG, Dr
Hôpital Saint-André, CHRU Bordeaux	Recruiting
Bordeaux, France, 33075
Contact: Hervé TRILLAUD, Pr 05 56 79 58 00 ext 33 herve.trillaud@chu-bordeaux.fr
Principal Investigator: Hervé TRILLAUD, Pr
Sub-Investigator: Hervé LAUMONIER, Dr
Sub-Investigator: Denis SMITH, Dr
Sub-Investigator: Jean Frédéric BLANC, Dr
CRLCC, Centre René Gauducheau	Recruiting
Nantes St Herblain, France, 44805
Contact: Catherine LABBE, Dr 33 2 40 67 99 89 c-labbe@nantes.fnclcc.fr
Principal Investigator: Catherine LABBE-DEVILLIERS, Dr
Sub-Investigator: Philippe MEINGAN, Dr
Sub-Investigator: Jean Yves DOUILLARD, Pr
Sub-Investigator: Stéphanie BORDENAVE-CAFFRE, Dr
Sub-Investigator: Hélène SENELLART, Dr
Sub-Investigator: Jaafar BENNOUNA, Dr
Hôpital Pitié Salpétrière, Assistance Publique Hôpitaux de Paris	Recruiting
Paris, France, 75651
Contact: Olivier LUCIDARME, Dr 33 1 42 17 63 06 olivier.lucidarme@psl.ap-hop-paris.fr
Principal Investigator: Olivier LUCIDARME, Dr
Sub-Investigator: Jean Pierre SPANO, Pr
Sub-Investigator: Julien TAIEB, Dr
Sub-Investigator: Amani ASNACIOS, Dr
Sub-Investigator: Samy LOUAFI, Dr
Hôpital Haut-Lévêque	Recruiting
Pessac, France, 33604
Contact: Jacques DROUILLARD, Pr 33 5.57.65.64.44 jacques.drouillard@chu-bordeaux.fr
Principal Investigator: Jacques DROUILLARD, Pr
Sub-Investigator: Benoit DIRIS, Dr
Sub-Investigator: Delphine GAYE, Dr
Hôpital La Milétrie, CHRU Poitiers	Recruiting
Poitiers, France, 86000
Contact: Jean-Pierre TASU, Pr 33 5 49 44 44 32 j.p.tasu@chu-poitiers.fr
Contact: Aurélie FERRU, Dr 33 5 49 44 45 38 a.ferru@chu-poitiers.fr
Principal Investigator: Jean-Pierre TASU, Pr
Sub-Investigator: Jérôme ROUMY, Dr
Sub-Investigator: Aurélie FERRU, Dr
Sub-Investigator: Frédéric FRUGE, Dr
Sub-Investigator: Claire CHARPIGNON, Dr
Hôpital Robert Debré, CHRU Reims	Recruiting
Reims, France, 51092
Contact: Claude MARCUS, Pr 33 3 26 78 42 16 cmarcus@chu-reims.fr
Contact: Viviane LADAM-MARCUS, Dr 33 3 26 78 42 16 vladammarcus@chu-reims.fr
Principal Investigator: Claude MARCUS, Pr
Sub-Investigator: Viviane LADAM-MARCUS, Dr
Sub-Investigator: Olivier BOUCHE, Pr
Sub-Investigator: Stéphanie LAGARDE, Dr
CHU Pontchaillou	Recruiting
Rennes, France, 35033
Contact: Sylvain MANFREDI, Dr 33 2 99 28 43 17 sylvain.manfredi@chu-rennes.fr
Principal Investigator: Sylvain MANFREDI, Dr
Sub-Investigator: Damien OLIVIE, Dr
CRLCC, Centre Eugène Marquis	Not yet recruiting
Rennes, France, 35042
Contact: Jean Luc RAOUL, Pr 33 2 99 25 31 96 raoul@rennes.fnclcc.fr
Principal Investigator: Jean Luc RAOUL, Pr
Sub-Investigator: Evelyne BOUCHER, Dr
Chru Tours	Recruiting
Tours, France, 37044
Contact: Thierry LECOMTE, Doctor 33 2 47 47 59 00 lecomt_t@med.univ-tours.fr
Contact: , Doctor
Principal Investigator: Thierry LECOMTE, Doctor
Sub-Investigator: Aurore BLEUZEN, Doctor
Sub-Investigator: Etienne DORVAL, Professor
Sub-Investigator: Jérôme VIGUIER, Doctor
Sub-Investigator: Sophie CHAPET, Doctor
Sub-Investigator: Bérengère NARCISO, Doctor

Sponsors and Collaborators

University Hospital, Tours

Investigators

Principal Investigator:	François TRANQUART, Professor	Centre Hospitalier de Tours, France
Principal Investigator:	Thierry LECOMTE, Doctor	Centre Hospitalier de Tours, France
Study Chair:	Bruno GIRAUDEAU, Doctor	INSERM CIC 2002, Centre Hospitalier de Tours, France
Study Chair:	Emmanuel RUSCH, Professor	Centre Hospitalier de Tours, France

More Information

Publications:

Bleuzen A, Huang C, Olar M, Tchuenbou J, Tranquart F. Diagnostic accuracy of contrast-enhanced ultrasound in focal lesions of the liver using cadence contrast pulse sequencing. Ultraschall Med. 2006 Feb;27(1):40-8.

Forsberg F, Ro RJ, Potoczek M, Liu JB, Merritt CR, James KM, Dicker AP, Nazarian LN. Assessment of angiogenesis: implications for ultrasound imaging. Ultrasonics. 2004 Apr;42(1-9):325-30.

Broillet A, Hantson J, Ruegg C, Messager T, Schneider M. Assessment of microvascular perfusion changes in a rat breast tumor model using SonoVue to monitor the effects of different anti-angiogenic therapies. Acad Radiol. 2005 May;12 Suppl 1:S28-33. No abstract available.

Niermann KJ, Fleischer AC, Donnelly EF, Schueneman AJ, Geng L, Hallahan DE. Sonographic depiction of changes of tumor vascularity in response to various therapies. Ultrasound Q. 2005 Jun;21(2):61-7; quiz 149, 153-4.

Preda A, Novikov V, Moglich M, Turetschek K, Shames DM, Brasch RC, Cavagna FM, Roberts TP. MRI monitoring of Avastin antiangiogenesis therapy using B22956/1, a new blood pool contrast agent, in an experimental model of human cancer. J Magn Reson Imaging. 2004 Nov;20(5):865-73.

Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005 Feb 1;65(3):671-80.

Zondor SD, Medina PJ. Bevacizumab: an angiogenesis inhibitor with efficacy in colorectal and other malignancies. Ann Pharmacother. 2004 Jul-Aug;38(7-8):1258-64. Epub 2004 Jun 8. Review.

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.

Responsible Party:	Directrice de la Recherche et des Affaires Médicales, University Hospital Tours
ClinicalTrials.gov Identifier:	NCT00489697 History of Changes
Other Study ID Numbers:	INCA06-FT/STIC-AVASTIN
Study First Received:	June 20, 2007
Last Updated:	February 19, 2009
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Tours:

colorectal cancer
hepatic metastases
bevacizumab
anti-angiogenic agent

chemotherapy regimens
tumor vascularity
Contrast-enhanced ultrasound

Additional relevant MeSH terms:

Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

Neoplastic Processes
Pathologic Processes
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013