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

Sponsor

St. Olavs Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03477019

Collaborator

(none)

Enrollment

Location

Arms

45.6

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms Breast Neoplasms	Drug: SonoVue Procedure: Focused Ultrasound	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 12, 2018

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Breast cancer target lesion 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 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. Procedure: Focused Ultrasound ultrasound pulses will be generated by a clinically approved ultrasound skanner and probe.
Other: Breast cancer control lesion This arm will only receive treatment with conventional chemotherapy for breastcancer and microbubbles intravenously.	Drug: SonoVue 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.
Experimental: Colorectal cancer target lesion 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 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. Procedure: Focused Ultrasound ultrasound pulses will be generated by a clinically approved ultrasound skanner and probe.
Other: Colorectal cancer control lesion This arm will only receive treatment with conventional chemotherapy for colorectal cancer and microbubbles intravenously.	Drug: SonoVue 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.

Outcome Measures

Primary Outcome Measures

difference in measured response between treated and untreated lesions [From baseline examination CT to response evaluation CT: 10-12 weeks]
Response is measured in change in size of the treated metastases.

Secondary Outcome Measures

Occurrence of adverse effects [8 weeks]
questionnaire 'Common toxicity criteria'

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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