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

NCT00489697 | Completed

• 1 other identifier: INCA06-FT/STIC-AVASTIN
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Metastatic Colorectal Cancer

Keywords

colorectal cancer; hepatic metastases; bevacizumab; anti-angiogenic agent; chemotherapy regimens; tumor vascularity; Contrast-enhanced ultrasound

Outcome Measures

Primary Outcomes (4)

• functional vascular changes in tumour vascularity of hepatic metastases

  2 months

• Pharmacokinetic of bevacizumab between each cure of bevacizumab based chemotherapy

  2 months

• ratio cost/benefit of a strategy of therapeutic monitoring by contrast-enhanced ultrasound

  2 months

• evaluation of the response to bevacizumab based chemotherapy by RECIST criteria

  2 months

Secondary Outcomes (4)

• bevacizumab-related toxicity

  2 months

• response duration

  2 years

• time to disease progression

  2 years

• survival time

  2 years

Study Arms (1)

1 (single arm)

EXPERIMENTAL

patient with histologically confirmed colorectal tumor treated in first line by a bevacizumab based chemotherapy

Device: real-time contrast-enhanced ultrasound imaging (CEUS)

Interventions

real-time contrast-enhanced ultrasound imaging (CEUS) DEVICE

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)

1 (single arm)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (12)

CHRU d'ANGERS

Angers, 49033, France

Location

CRLCC, Centre Paul Papin

Angers, 49033, France

Location

CHRU Besancon

Besançon, 25000, France

Location

Hôpital Saint-André, CHRU Bordeaux

Bordeaux, 33075, France

Location

CRLCC, Centre René Gauducheau

Nantes Saint Herblain, 44805, France

Location

Hôpital Pitié Salpétrière, Assistance Publique Hôpitaux de Paris

Paris, 75651, France

Location

Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Hôpital La Milétrie, CHRU Poitiers

Poitiers, 86000, France

Location

Hôpital Robert Debré, CHRU Reims

Reims, 51092, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

CRLCC, Centre Eugène Marquis

Rennes, 35042, France

Location

Chru Tours

Tours, 37044, France

Location

Related Publications (11)

• 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. doi: 10.1055/s-2005-858944.

  PMID: 16470478 BACKGROUND

• 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. doi: 10.1016/j.ultras.2003.12.026.

  PMID: 15047306 BACKGROUND

• 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. doi: 10.1016/j.acra.2005.02.021. No abstract available.

  PMID: 16106543 BACKGROUND

• 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.

  PMID: 15905816 BACKGROUND

• 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. doi: 10.1002/jmri.20184.

  PMID: 15503324 BACKGROUND

• 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.

  PMID: 15705858 BACKGROUND

• 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. doi: 10.1345/aph.1D470. Epub 2004 Jun 8.

  PMID: 15187215 BACKGROUND

• 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.

  PMID: 15175435 BACKGROUND

• Mazard T, Mollevi C, Loyer EM, Leger J, Chautard R, Bouche O, Borg C, Armand-Dujardin P, Bleuzen A, Assenat E, Lecomte T. Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial. Cancer Imaging. 2024 Jun 17;24(1):77. doi: 10.1186/s40644-024-00722-7.

  PMID: 38886836 DERIVED

• Lobet S, Caulet M, Paintaud G, Azzopardi N, Desvignes C, Chautard R, Borg C, Capitain O, Ferru A, Bouche O, Lecomte T, Ternant D. Confounding mitigation for the exposure-response relationship of bevacizumab in colorectal cancer patients. Br J Clin Pharmacol. 2024 Apr;90(4):976-986. doi: 10.1111/bcp.15983. Epub 2023 Dec 29.

  PMID: 38072829 DERIVED

• Jary M, Lecomte T, Bouche O, Kim S, Dobi E, Queiroz L, Ghiringhelli F, Etienne H, Leger J, Godet Y, Balland J, Lakkis Z, Adotevi O, Bonnetain F, Borg C, Vernerey D. Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score. Int J Cancer. 2016 Nov 15;139(10):2325-35. doi: 10.1002/ijc.30367. Epub 2016 Aug 13.

  PMID: 27472156 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• François TRANQUART, Professor

  Centre Hospitalier de Tours, France

  PRINCIPAL INVESTIGATOR

• Thierry LECOMTE, Doctor

  Centre Hospitalier de Tours, France

  PRINCIPAL INVESTIGATOR

• Bruno GIRAUDEAU, Doctor

  INSERM CIC 2002, Centre Hospitalier de Tours, France

  STUDY CHAIR

• Emmanuel RUSCH, Professor

  Centre Hospitalier de Tours, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 21, 2007
• Study Start: January 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: January 4, 2017

Record last verified: 2017-01

Locations

FR (12)