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Targeted Delivery of Chemotherapy With Ultrasound and Microbublles (SONCHIMIO)

Primary Purpose

Colorectal Cancer, Hepatic Metastases

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
MRI
Perfusion CT scan
Contrast enhanced ultrasound
Sonoporation
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring microbubbles, sonoporation, hepatic metastases of colorectal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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);
  • Previous malignancy other than colorectal adenocarcinoma within 3 years prior to the inclusion with the exception for curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer;
  • 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;
  • Inclusion in another therapeutic trial
  • 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

Sites / Locations

  • Service d'Hépatogastro-entérologie CHRU de TOURS

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Selected liver metastases of the patient

Not-selected liver metastases of the patient

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Safety
Safety based on National Cancer Institute (NCI), Common Terminology Criteria for Adverse events (CTCAE)
Tolerance
Tolerance based on National Cancer Institute (NCI), Common Terminology Criteria for Adverse events (CTCAE)
Maximum percent reduction in tumor density on CT scan
Maximum percent reduction in tumor density (Hounsfield units) from baseline
Maximum percent reduction in tumor density on MRI
Maximum percent reduction in tumor density from baseline
Assessment of tumor vascularity by Perfusion CT scan
Assessment of tumor vascularity with Perfusion CT scan
Assessment of tumor vascularity by MRI
Assessment of tumor vascularity with MRI
Assessment of tumor vascularity by Dynamic Contrast-Enhanced US (DCE-US)
Assessment of tumor vascularity with Dynamic Contrast-Enhanced US (DCE-US)
Dosage of antibody anti-VEGF or anti-EGFR
Measures of serum concentration of antibody anti-VEGF or anti-EGFR
Dosage of antibody anti-VEGF or anti-EGFR by ELISA test
Pharmacokinetic of antibody anti-VEGF or anti-EGFR
Dosage of cytokines
Dosage of cytokines

Full Information

First Posted
March 2, 2018
Last Updated
January 6, 2023
Sponsor
University Hospital, Tours
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1. Study Identification

Unique Protocol Identification Number
NCT03458975
Brief Title
Targeted Delivery of Chemotherapy With Ultrasound and Microbublles
Acronym
SONCHIMIO
Official Title
Targeted Delivery of Chemotherapy With Ultrasound and Microbubbles
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
September 30, 2022 (Actual)
Study Completion Date
September 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Hepatic Metastases
Keywords
microbubbles, sonoporation, hepatic metastases of colorectal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Selected liver metastases of the patient
Arm Type
Active Comparator
Arm Description
Liver metastases randomized to receive sonoporation (US waves + gaseous microbubbles). The patient continue to receive the usual systemic chemotherapy
Arm Title
Not-selected liver metastases of the patient
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
MRI
Intervention Description
Magnetic Resonance Imaging
Intervention Type
Radiation
Intervention Name(s)
Perfusion CT scan
Intervention Description
Perfusion Computerized tomography scan
Intervention Type
Other
Intervention Name(s)
Contrast enhanced ultrasound
Intervention Description
Contrast enhanced ultrasound
Intervention Type
Drug
Intervention Name(s)
Sonoporation
Intervention Description
Gaseous microbubbles (Sonovue) combinated with Ultrasounds
Primary Outcome Measure Information:
Title
Objective response for liver metastases
Description
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
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Safety
Description
Safety based on National Cancer Institute (NCI), Common Terminology Criteria for Adverse events (CTCAE)
Time Frame
Day 3, Day 17, Day 32, Day 47
Title
Tolerance
Description
Tolerance based on National Cancer Institute (NCI), Common Terminology Criteria for Adverse events (CTCAE)
Time Frame
Day 3, Day 17, Day 32, Day 47
Title
Maximum percent reduction in tumor density on CT scan
Description
Maximum percent reduction in tumor density (Hounsfield units) from baseline
Time Frame
2 months
Title
Maximum percent reduction in tumor density on MRI
Description
Maximum percent reduction in tumor density from baseline
Time Frame
2 months
Title
Assessment of tumor vascularity by Perfusion CT scan
Description
Assessment of tumor vascularity with Perfusion CT scan
Time Frame
2 months
Title
Assessment of tumor vascularity by MRI
Description
Assessment of tumor vascularity with MRI
Time Frame
2 months
Title
Assessment of tumor vascularity by Dynamic Contrast-Enhanced US (DCE-US)
Description
Assessment of tumor vascularity with Dynamic Contrast-Enhanced US (DCE-US)
Time Frame
2 months
Title
Dosage of antibody anti-VEGF or anti-EGFR
Description
Measures of serum concentration of antibody anti-VEGF or anti-EGFR
Time Frame
Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Title
Dosage of antibody anti-VEGF or anti-EGFR by ELISA test
Description
Pharmacokinetic of antibody anti-VEGF or anti-EGFR
Time Frame
Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Title
Dosage of cytokines
Description
Dosage of cytokines
Time Frame
Day1, Day 3, Day 15, Day 17, Day 32, Day 45

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). Exclusion Criteria: 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); Previous malignancy other than colorectal adenocarcinoma within 3 years prior to the inclusion with the exception for curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer; 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; Inclusion in another therapeutic trial 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
Facility Information:
Facility Name
Service d'Hépatogastro-entérologie CHRU de TOURS
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Targeted Delivery of Chemotherapy With Ultrasound and Microbublles

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