Ultrasound-enhanced Delivery of Chemotherapy to Patients With Liver Metastasis From Breast- and Colorectal Cancer

Study Overview
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Brief Summary
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The aim of this clinical trial is to investigate whether the therapeutic response of chemotherapy can be improved by focused ultrasound and microbubbles. Patients with liver metastases from breast cancer and colorectal cancer will be included. Computer Tomography (CT) will be performed as a baseline scan before treatment start. Two metastases in each patients liver will be preselected and randomized to either target lesion to be treated or control lesion to serve as internal control. The patients will receive conventional treatment with chemotherapy according to national guidelines. After intravenous chemotherapy infusion the patients will receive the experimental treatment. The target lesion will get focused ultrasound (FUS). Simultaneously repeated bolus-doses of microbubbles will be administered intravenously. The investigators will measure the difference in response between FUS- treated and -untreated lesions on the post-treatment CT scan.

Official Title
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Ultrasound-enhanced Delivery of Chemotherapy to Patients With Liver Metastasis From Breast- and Colorectal Carcinoma- a Randomized Trial

Conditions
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Colorectal Neoplasms, Breast Neoplasms

Intervention / Treatment
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* Drug: SonoVue
* Procedure: Focused Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified breast carcinoma or colorectal carcinoma 2 or multiple liver metastases considered eligible by a consulting oncologist for first line treatment with chemotherapy in the group of taxanes (patients with breast cancer) or the combination regimen FOLFIRI (patients with colorectal carcinoma) Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations Exclusion Criteria: Known contraindications for ultrasound contrast-enhancement agent Sonovue® (Bracco) Hematological bleeding status before experimental treatment: Hb < 8g/dL, trc < 80 x109/l, APTT˃ 45s, INR ˃ 1,5 Considered eligible for surgical removal of liver metastases Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two liver metastases in every patient are preselected on baseline computer tomography. These will be randomized to either 1) target lesion to be treated or 2) control lesion. Difference in response (pre- and post-treatment measure) between treated lesions and control lesions will be the primary outcome of the trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breast cancer target lesion<br>This arm will receive experimental treatment of focused ultrasound. In addition this arm will receive treatment with microbubbles intravenously and conventional chemotherapy for breast cancer. | Drug: SonoVue<br>* consists of microbubbles containing sulfur hexafluoride stabilized by phospholipids. Bolus doses à 1,0ml administered every 3.5 minutes , repeated 9 times. Total duration of treatment: 31,5 minutes. This treatment will be repeated maximally 4 times at 2 or 3 week intervals, depending on the patient's diagonse and treatment protocol.<br>Procedure: Focused Ultrasound<br>* ultrasound pulses will be generated by a clinically approved ultrasound skanner and probe.<br>|
| Other: Breast cancer control lesion<br>This arm will only receive treatment with conventional chemotherapy for breastcancer and microbubbles intravenously. | Drug: SonoVue<br>* consists of microbubbles containing sulfur hexafluoride stabilized by phospholipids. Bolus doses à 1,0ml administered every 3.5 minutes , repeated 9 times. Total duration of treatment: 31,5 minutes. This treatment will be repeated maximally 4 times at 2 or 3 week intervals, depending on the patient's diagonse and treatment protocol.<br>|
| Experimental: Colorectal cancer target lesion<br>This arm will receive experimental treatment of focused ultrasound. In addition this arm will receive treatment with microbubbles intravenously and conventional chemotherapy for colorectal cancer. | Drug: SonoVue<br>* consists of microbubbles containing sulfur hexafluoride stabilized by phospholipids. Bolus doses à 1,0ml administered every 3.5 minutes , repeated 9 times. Total duration of treatment: 31,5 minutes. This treatment will be repeated maximally 4 times at 2 or 3 week intervals, depending on the patient's diagonse and treatment protocol.<br>Procedure: Focused Ultrasound<br>* ultrasound pulses will be generated by a clinically approved ultrasound skanner and probe.<br>|
| Other: Colorectal cancer control lesion<br>This arm will only receive treatment with conventional chemotherapy for colorectal cancer and microbubbles intravenously. | Drug: SonoVue<br>* consists of microbubbles containing sulfur hexafluoride stabilized by phospholipids. Bolus doses à 1,0ml administered every 3.5 minutes , repeated 9 times. Total duration of treatment: 31,5 minutes. This treatment will be repeated maximally 4 times at 2 or 3 week intervals, depending on the patient's diagonse and treatment protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference in measured response between treated and untreated lesions | Response is measured in change in size of the treated metastases. | From baseline examination CT to response evaluation CT: 10-12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse effects | questionnaire 'Common toxicity criteria' | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contrast Agent BR, SonoVue, Ultrasonic Therapy, Neoplasm Metastasis, Liver, Microbubbles