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

NCT03477019 | Completed Phase 1

• 2 other identifiers: 2018/132018-002814-11
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Neoplasms; Breast Neoplasms

Keywords

Contrast Agent BR; SonoVue; Ultrasonic Therapy; Neoplasm Metastasis; Liver; Microbubbles

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Occurrence of adverse effects

  8 weeks

Study Arms (4)

Breast cancer target lesion

EXPERIMENTAL

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; Procedure: Focused Ultrasound

Breast cancer control lesion

OTHER

This arm will only receive treatment with conventional chemotherapy for breastcancer and microbubbles intravenously.

Drug: SonoVue

Colorectal cancer target lesion

EXPERIMENTAL

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; Procedure: Focused Ultrasound

Colorectal cancer control lesion

OTHER

This arm will only receive treatment with conventional chemotherapy for colorectal cancer and microbubbles intravenously.

Drug: SonoVue

Interventions

SonoVue DRUG

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.

Breast cancer control lesion; Breast cancer target lesion; Colorectal cancer control lesion; Colorectal cancer target lesion

Focused Ultrasound PROCEDURE

ultrasound pulses will be generated by a clinically approved ultrasound skanner and probe.

Breast cancer target lesion; Colorectal cancer target lesion

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically verified breast carcinoma or colorectal carcinoma
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Olavs Hospital: lead

Study Sites (1)

St.Olavs Hospital

Trondheim, Norway

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Breast Neoplasms; Neoplasm Metastasis

Interventions

contrast agent BR1

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arne Solberg, PhD, MD

  St. Olavs Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: March 26, 2018
• Study Start: November 12, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: January 19, 2023

Record last verified: 2023-01

Locations

NO (1)