Ultrasound Liver Intraoperative Imaging With SonoVue® (ULIIS)

Clinical Utility of Contrast-enhanced Intraoperative Ultrasound in Surgery of Colorectal Liver Metastases. Phase II Clinical Trial.

Hypothesis: Use of contrast ultrasound showed interesting results, which can increase ultrasonography sensitivity performed during surgery in the evaluation of operable liver metastases.

This study is a two-stage phase II multicenter study (Simon's two-stage).

Study Overview

• Status: Completed
• Conditions: Liver Metastases From Colorectal Primary Cancer
• Intervention / Treatment: Device: Contrast-enhanced intraoperative ultrasound

Detailed Description

Hypothesis: Use of contrast ultrasound showed interesting results, which can increase ultrasonography sensitivity performed during surgery in the evaluation of operable liver metastases.

This study is a two-stage phase II multicenter study (Simon's two-stage).

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33000
      • Institut Bergonie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient with histological proven colorectal cancer.
2. Operable liver metastases according to preoperative imagery. Operability is the possibility of treatment by resection and/or local destruction (radiofrequency, cryotherapy…).
3. Patient treated or not with preoperative chemotherapy.
4. With or without extra-hepatic metastases
5. Age ≥ 18 years.
6. Radiological assessment by CT and MRI liver and positron emission tomography scan (PETscan) within six weeks before surgery.
7. Patient affiliated to the Social Security system.
8. Signed informed consent.

Exclusion Criteria:

1. Known hypersensitivity to sulfur hexafluoride or another component of SonoVue®.
2. Patients with recent acute coronary syndrome or suffering from unstable ischemic heart disease, especially: evolving myocardial infarction, unstable angina during the last 7 days, recent coronary intervention or another factor suggesting clinical instability, acute heart failure, class III or IV heart failure, severe arrhythmias.
3. Patients with right-to-left shunt, severe pulmonary arterial hypertension, uncontrolled systemic hypertension, as patients suffering from respiratory distress syndrome.
4. Pregnant and lactating women.
5. Patients with contraindication for a CT scan, a MRI or a positron emission tomography (PET) with contrast.
6. Patients with indication of two step liver surgery.
7. Patients already included in the study.
8. Patient who couldn't be treated or followed up according to study criteria for psychological, social, family or geographical reasons. Patient deprived of liberty or under guardianship.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Contrast-enhanced intraoperative ultrasound	Device: Contrast-enhanced intraoperative ultrasound; Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Utility of Intraoperative Contrast Ultrasound in the Surgery of Colorectal Cancer Liver Metastases.	The clinical utility will be evaluated in terms of justified modification of the surgical procedure following contrast-enhanced intra-operative ultrasound (CE-IOUS), compared to the surgical procedure following conventional intra-operative ultrasound. For each patient, we will consider CE-IOUS to be clinically useful: if the surgical procedure envisaged at the end of the CE-IOUS is different from the surgical procedure envisaged at the end of the conventional ultrasound; and if the surgical procedure envisaged at the end of the CE-IOUS is justified We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS.	At time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Utility of CE-IOUS in Subgroup of Patients Who Received Preoperative Chemotherapy	The primary endpoint will be assessed in the subgroup of patients who received preoperative chemotherapy. As for the primary outcome, the clinical utility is evaluated in terms of justified modification of the surgical gesture envisaged following CE-IOUS, compared to the surgical gesture envisaged following a conventional intraoperative ultrasound. We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS in the subgroup of patients who received preoperative chemotherapy.	at time of surgery
Performance Evaluation of Intraoperative Ultrasound Contrast: Detection Rate Per Lesion	Detection of malignant lesions by CE-IOUS in chemotherapy-free patients within 3 post-operative months. The detection rate is defined as the proportion of malignant lesions for which there is concordance between the diagnosis established by CE-IOUS and the reference examination.	up to 3 months after surgery
Description of Technical Arrangements for the CE-IOUS	Description of technical arrangements for the CE-IOUS duration. The length of time during which contrast injection was useable.	At time of contrast-enhanced IOUS
Performance Evaluation of Intraoperative Ultrasound Contrast Per Lesion: Characterisation Rate	Characterisation rate for focal liver lesions: the proportion of lesions whose nature on CE-IOUS is identical to the nature of the lesions defined by the reference examinations among all the lesions seen on CE-IOUS (malignant and benign)	up to 3 months after surgery

Collaborators and Investigators

• Sponsor: Institut Bergonié
• Investigators: Study Chair: EVRARD Serge, PU-PH, Institut Bergonie

Publications and helpful links

General Publications

• Desolneux G, Isambert M, Mathoulin-Pelissier S, Dupre A, Rivoire M, Cattena V, Palussiere J, Dinart D, Bellera C, Evrard S. Contrast-enhanced intra-operative ultrasound as a clinical decision making tool during surgery for colorectal liver metastases: The ULIIS study. Eur J Surg Oncol. 2019 Jul;45(7):1212-1218. doi: 10.1016/j.ejso.2019.03.002. Epub 2019 Mar 10.

Helpful Links

• French national cancer institute (INCa) Clinical Trials Registry
• Website of the sponsor

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: November 5, 2012
• First Submitted That Met QC Criteria: June 14, 2013
• First Posted (Estimated): June 19, 2013

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 22, 2025
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Contrast-enhanced ultrasound; Liver metastases; Colorectal primary cancer; Sonovue®
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: IB2010-29