Clinical trial NCT00489697: 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
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Colorectal Cancer
Keywords: colorectal cancer
hepatic metastases
bevacizumab
anti-angiogenic agent
chemotherapy regimens
tumor vascularity
Contrast-enhanced ultrasound
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2007-06-21
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: functional vascular changes in tumour vascularity of hepatic metastases
timeFrame: 2 months
measure: Pharmacokinetic of bevacizumab between each cure of bevacizumab based chemotherapy
timeFrame: 2 months
measure: ratio cost/benefit of a strategy of therapeutic monitoring by contrast-enhanced ultrasound
timeFrame: 2 months
measure: evaluation of the response to bevacizumab based chemotherapy by RECIST criteria
timeFrame: 2 months
Secondary outcomes:
measure: bevacizumab-related toxicity
timeFrame: 2 months
measure: response duration
timeFrame: 2 years
measure: time to disease progression
timeFrame: 2 years
measure: survival time
timeFrame: 2 years
Other outcomes:
Locations:
city: Angers
country: France
facility: CHRU d'ANGERS
city: Angers
country: France
facility: CRLCC, Centre Paul Papin
city: Besançon
country: France
facility: CHRU Besancon
city: Bordeaux
country: France
facility: Hôpital Saint-André, CHRU Bordeaux
city: Nantes St Herblain
country: France
facility: CRLCC, Centre René Gauducheau
city: Paris
country: France
facility: Hôpital Pitié Salpétrière, Assistance Publique Hôpitaux de Paris
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Poitiers
country: France
facility: Hôpital La Milétrie, CHRU Poitiers
city: Reims
country: France
facility: Hôpital Robert Debré, CHRU Reims
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rennes
country: France
facility: CRLCC, Centre Eugène Marquis
city: Tours
country: France
facility: Chru Tours
Study officials:
affiliation: Centre Hospitalier de Tours, France
name: François TRANQUART, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier de Tours, France
name: Thierry LECOMTE, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM CIC 2002, Centre Hospitalier de Tours, France
name: Bruno GIRAUDEAU, Doctor
role: STUDY_CHAIR
affiliation: Centre Hospitalier de Tours, France
name: Emmanuel RUSCH, Professor
role: STUDY_CHAIR
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