Targeted Delivery of Chemotherapy With Ultrasound and Microbublles

Last updated: January 6, 2023
Sponsor: University Hospital, Tours
Overall Status: Completed

Phase

2

Condition

Rectal Cancer

Colorectal Cancer

Colon Cancer

Treatment

N/A

Clinical Study ID

NCT03458975
PRTK15-TL/SONCHIMIO
  • Ages > 18
  • All Genders

Study Summary

The oscillations of ultrasound (US) contrast agent microbubbles under their activation by US waves engender a modulation of the permeability of biological barriers amplifying hence the extravasation of drugs and/or fluorescent markers through a process known as sonoporation. In such a way, the bioavailability of the therapeutic agent is augmented only in the area where US waves are focused. The objective now is to translate this therapeutic approach to the clinic by performing a feasibility study with the development of a therapy regime optimized for hepatic metastases of colorectal cancer.

In order to demonstrate the clinical feasibility of the therapeutic approach based on ultrasound and microbubbles, we will focus on patients with liver metastases of colorectal cancer treated with monoclonal antibodies in combination with chemotherapy.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • patient with liver metastases from colorectal cancer; patient with minimum two livermetastases which satisfy all the following criteria: diameter between 10 and 35 mm;arterially enhancing liver metastases detected with contrast enhanced ultrasound (CEUS); measurable liver metastases with CT-scan (Acceptability of a patient with morethan 4 metastases or a patient with an odd number of metastases ≥ 2).
  • age ≥ 18 years;
  • ECOG/OMS 0-1;
  • life expectancy of at least 12 weeks;
  • adequate bone marrow, liver and kidney function;
  • written informed consent obtained from subject;
  • subjects covered by or having the rights to social security;
  • bi-weekly chemotherapy regimen
  • neo-adjuvant standard chemotherapy or palliative standard chemotherapy (first orsecond metastatic line) following the recommendations in force (national thesaurus ofdigestive oncology - colorectal cancer chapter: Phelip JM, Benhaim L, Bouché O,Christou N, Desolneux G, Dupré A, Léonard D, Michel P, Penna C, Rousseaux B, TougeronD, Tournigand C. "Cancer colorectal métastatique". Thésaurus National de CancérologieDigestive, Janvier 2019, http://www.tncd.org).

Exclusion

Exclusion Criteria:

  • Previous local treatment of selected liver metastases (radiofrequency,radioembolization, …);
  • Indication for local ablative therapy of selected liver metastasis (radiofrequencyablation or other validated hepatic-directed modality of treatment);
  • Previous malignancy other than colorectal adenocarcinoma within 3 years prior to theinclusion with the exception for curatively treated basal cell carcinoma of the skinand/or curatively resected in situ cervical or breast cancer;
  • Known contraindication to the injection of Sonovue®, of Gadolinium, of iodatedcontrast agent;
  • contraindication to MRI or perfusion CT scan;
  • Patient under legal protection;
  • Pregnant or lactating woman, or woman with ability to procreate and withoutcontraception;
  • Inclusion in another therapeutic trial
  • Uracilemia greater than or equal to 150ng/mL (suggestive of a complete DPDdeficiency).
  • Presence of any material with potential interaction with ultrasound beam (metal, etc.)or healing tissue, and which cannot be bypassed

Study Design

Total Participants: 7
Study Start date:
October 01, 2019
Estimated Completion Date:
September 30, 2022

Study Description

Despite the increasing number of active molecules and the availability of news targeted therapies for cancer, therapeutic achievements remain modest for a number of tumor types. One of the major obstacles is inherent to the absence of specific delivery in the tumor tissue.

We have demonstrated recently that the oscillations of ultrasound (US) contrast agent microbubbles under their activation by US waves engender a modulation of the permeability of biological barriers amplifying hence the extravasation of drugs and/or fluorescent markers through a process known as sonoporation. In such a way, the bioavailability of the therapeutic agent is augmented only in the area where US waves are focused. The objective now is to translate this therapeutic approach to the clinic by performing a feasibility study with the development of a therapy regime optimized for hepatic metastases of colorectal cancer.

In order to demonstrate the clinical feasibility of the therapeutic approach based on ultrasound and microbubbles, we will focus on patients with liver metastases of colorectal cancer treated with monoclonal antibodies in combination with chemotherapy.

The work aims into evaluating the therapeutic efficacy of the proposed approach on a number of selected patients. We will follow the usual treatment schemes and we will apply imaging protocols to visualize tumor progression.

This technique of optimization of the intratumoral availability of anticancer drugs and based on sonoporation will improve the efficacy and safety of systemic chemotherapy by providing increased tumor uptake relative to normal tissue. This technique provides an ideal and easy strategy to optimize intratumoral drug delivery.

Connect with a study center

  • Service d'Hépatogastro-entérologie CHRU de TOURS

    Tours, 37044
    France

    Site Not Available

Map preview placeholder

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.