Evaluation of Contrast-enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases

Metastatic Colorectal Cancer Clinical Trial

Official title:

Medical and Economical Evaluation of Contrast-enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00489697
• Other study ID #: INCA06-FT/STIC-AVASTIN
• Status: Completed
• Phase: N/A
• First received: June 20, 2007
• Last updated: January 2, 2017
• Start date: January 2007
• Est. completion date: November 2012

Study information

• Verified date: January 2017
• Source: University Hospital, Tours
• 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer
• Neoplasm Metastasis

Intervention

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)

Locations

Country	Name	City	State
France	CHRU d'ANGERS	Angers
France	CRLCC, Centre Paul Papin	Angers
France	CHRU Besancon	Besançon
France	Hôpital Saint-André, CHRU Bordeaux	Bordeaux
France	CRLCC, Centre René Gauducheau	Nantes St Herblain
France	Hôpital Pitié Salpétrière, Assistance Publique Hôpitaux de Paris	Paris
France	Hôpital Haut-Lévêque	Pessac
France	Hôpital La Milétrie, CHRU Poitiers	Poitiers
France	Hôpital Robert Debré, CHRU Reims	Reims
France	CHU Pontchaillou	Rennes
France	CRLCC, Centre Eugène Marquis	Rennes
France	Chru Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — 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

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. — View Citation

Preda A, Novikov V, Möglich 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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	functional vascular changes in tumour vascularity of hepatic metastases		2 months	No
Primary	Pharmacokinetic of bevacizumab between each cure of bevacizumab based chemotherapy		2 months	No
Primary	ratio cost/benefit of a strategy of therapeutic monitoring by contrast-enhanced ultrasound		2 months	No
Primary	evaluation of the response to bevacizumab based chemotherapy by RECIST criteria		2 months	No
Secondary	bevacizumab-related toxicity		2 months	Yes
Secondary	response duration		2 years	No
Secondary	time to disease progression		2 years	No
Secondary	survival time		2 years	No