Targeted Delivery of Chemotherapy With Ultrasound and Microbublles

NCT03458975 | Completed Phase 2 DMC

• 1 other identifier: PRTK15-TL/SONCHIMIO
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer; Hepatic Metastases

Keywords

microbubbles; sonoporation; hepatic metastases of colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Objective response for liver metastases

  Objective response for liver metastases with spiral CT scan and defined as decrease of at least 30% in the longer diameter of each selected liver metastases

  2 months

Secondary Outcomes (10)

• Safety

  Day 3, Day 17, Day 32, Day 47

• Tolerance

  Day 3, Day 17, Day 32, Day 47

• Maximum percent reduction in tumor density on CT scan

  2 months

• Maximum percent reduction in tumor density on MRI

  2 months

• Assessment of tumor vascularity by Perfusion CT scan

  2 months

Study Arms (2)

Selected liver metastases of the patient

ACTIVE COMPARATOR

Liver metastases randomized to receive sonoporation (US waves + gaseous microbubbles). The patient continue to receive the usual systemic chemotherapy

Radiation: MRI; Radiation: Perfusion CT scan; Other: Contrast enhanced ultrasound; Drug: Sonoporation

Not-selected liver metastases of the patient

PLACEBO COMPARATOR

Liver metatstases not randomized to receive sonoporation (US waves + gaseous microbubbles). The patient continue to receive the usual systemic chemotherapy like the active comparator arm

Radiation: MRI; Radiation: Perfusion CT scan; Other: Contrast enhanced ultrasound

Interventions

MRI RADIATION

Magnetic Resonance Imaging

Not-selected liver metastases of the patient; Selected liver metastases of the patient

Perfusion CT scan RADIATION

Perfusion Computerized tomography scan

Not-selected liver metastases of the patient; Selected liver metastases of the patient

Contrast enhanced ultrasound OTHER

Contrast enhanced ultrasound

Not-selected liver metastases of the patient; Selected liver metastases of the patient

Sonoporation DRUG

Gaseous microbubbles (Sonovue) combinated with Ultrasounds

Selected liver metastases of the patient

Eligibility Criteria

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

You may qualify if:

• patient with liver metastases from colorectal cancer; patient with minimum two liver metastases 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 more than 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 or second metastatic line) following the recommendations in force (national thesaurus of digestive oncology - colorectal cancer chapter: Phelip JM, Benhaim L, Bouché O, Christou N, Desolneux G, Dupré A, Léonard D, Michel P, Penna C, Rousseaux B, Tougeron D, Tournigand C. "Cancer colorectal métastatique". Thésaurus National de Cancérologie Digestive, Janvier 2019, http://www.tncd.org).

You may not qualify if:

• Previous local treatment of selected liver metastases (radiofrequency, radioembolization, …);
• Indication for local ablative therapy of selected liver metastasis (radiofrequency ablation or other validated hepatic-directed modality of treatment);
• Known contraindication to the injection of Sonovue®, of Gadolinium, of iodated contrast agent;
• contraindication to MRI or perfusion CT scan;
• Patient under legal protection;
• Pregnant or lactating woman, or woman with ability to procreate and without contraception;
• Uracilemia greater than or equal to 150ng/mL (suggestive of a complete DPD deficiency).
• Presence of any material with potential interaction with ultrasound beam (metal, etc.) or healing tissue, and which cannot be bypassed

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (1)

Service d'Hépatogastro-entérologie CHRU de TOURS

Tours, 37044, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: March 8, 2018
• Study Start: October 1, 2019
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: January 9, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)