search
Back to results

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

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
real-time contrast-enhanced ultrasound imaging (CEUS)
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Metastatic Colorectal Cancer focused on measuring colorectal cancer, hepatic metastases, bevacizumab, anti-angiogenic agent, chemotherapy regimens, tumor vascularity, Contrast-enhanced ultrasound

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHRU d'ANGERS
  • CRLCC, Centre Paul Papin
  • CHRU Besancon
  • Hôpital Saint-André, CHRU Bordeaux
  • CRLCC, Centre René Gauducheau
  • Hôpital Pitié Salpétrière, Assistance Publique Hôpitaux de Paris
  • Hôpital Haut-Lévêque
  • Hôpital La Milétrie, CHRU Poitiers
  • Hôpital Robert Debré, CHRU Reims
  • CHU Pontchaillou
  • CRLCC, Centre Eugène Marquis
  • Chru Tours

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1 (single arm)

Arm Description

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

Outcomes

Primary Outcome Measures

functional vascular changes in tumour vascularity of hepatic metastases
Pharmacokinetic of bevacizumab between each cure of bevacizumab based chemotherapy
ratio cost/benefit of a strategy of therapeutic monitoring by contrast-enhanced ultrasound
evaluation of the response to bevacizumab based chemotherapy by RECIST criteria

Secondary Outcome Measures

bevacizumab-related toxicity
response duration
time to disease progression
survival time

Full Information

First Posted
June 20, 2007
Last Updated
January 2, 2017
Sponsor
University Hospital, Tours
search

1. Study Identification

Unique Protocol Identification Number
NCT00489697
Brief Title
Evaluation of Contrast-enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases
Official Title
Medical and Economical Evaluation of Contrast-enhanced Ultrasound Imaging for the Early Estimate of Bevacizumab Effect on Colorectal Cancer Liver Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University Hospital, Tours

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
colorectal cancer, hepatic metastases, bevacizumab, anti-angiogenic agent, chemotherapy regimens, tumor vascularity, Contrast-enhanced ultrasound

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1 (single arm)
Arm Type
Experimental
Arm Description
patient with histologically confirmed colorectal tumor treated in first line by a bevacizumab based chemotherapy
Intervention Type
Device
Intervention Name(s)
real-time contrast-enhanced ultrasound imaging (CEUS)
Intervention Description
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)
Primary Outcome Measure Information:
Title
functional vascular changes in tumour vascularity of hepatic metastases
Time Frame
2 months
Title
Pharmacokinetic of bevacizumab between each cure of bevacizumab based chemotherapy
Time Frame
2 months
Title
ratio cost/benefit of a strategy of therapeutic monitoring by contrast-enhanced ultrasound
Time Frame
2 months
Title
evaluation of the response to bevacizumab based chemotherapy by RECIST criteria
Time Frame
2 months
Secondary Outcome Measure Information:
Title
bevacizumab-related toxicity
Time Frame
2 months
Title
response duration
Time Frame
2 years
Title
time to disease progression
Time Frame
2 years
Title
survival time
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
François TRANQUART, Professor
Organizational Affiliation
Centre Hospitalier de Tours, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thierry LECOMTE, Doctor
Organizational Affiliation
Centre Hospitalier de Tours, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bruno GIRAUDEAU, Doctor
Organizational Affiliation
INSERM CIC 2002, Centre Hospitalier de Tours, France
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Emmanuel RUSCH, Professor
Organizational Affiliation
Centre Hospitalier de Tours, France
Official's Role
Study Chair
Facility Information:
Facility Name
CHRU d'ANGERS
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
CRLCC, Centre Paul Papin
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
CHRU Besancon
City
Besançon
ZIP/Postal Code
25000
Country
France
Facility Name
Hôpital Saint-André, CHRU Bordeaux
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Facility Name
CRLCC, Centre René Gauducheau
City
Nantes St Herblain
ZIP/Postal Code
44805
Country
France
Facility Name
Hôpital Pitié Salpétrière, Assistance Publique Hôpitaux de Paris
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Hôpital Haut-Lévêque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Hôpital La Milétrie, CHRU Poitiers
City
Poitiers
ZIP/Postal Code
86000
Country
France
Facility Name
Hôpital Robert Debré, CHRU Reims
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
CHU Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
CRLCC, Centre Eugène Marquis
City
Rennes
ZIP/Postal Code
35042
Country
France
Facility Name
Chru Tours
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
16470478
Citation
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.
Results Reference
background
PubMed Identifier
15047306
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. doi: 10.1016/j.ultras.2003.12.026.
Results Reference
background
PubMed Identifier
16106543
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. doi: 10.1016/j.acra.2005.02.021. No abstract available.
Results Reference
background
PubMed Identifier
15905816
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.
Results Reference
background
PubMed Identifier
15503324
Citation
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.
Results Reference
background
PubMed Identifier
15705858
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.
Results Reference
background
PubMed Identifier
15187215
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. doi: 10.1345/aph.1D470. Epub 2004 Jun 8.
Results Reference
background
PubMed Identifier
15175435
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. doi: 10.1056/NEJMoa032691.
Results Reference
background
PubMed Identifier
27472156
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs