Colorectal CancerPhase 2SONCHIMIONCT03458975
Targeted Delivery of Chemotherapy With Ultrasound and Microbublles
A Phase 2 study testing MRI, Perfusion CT scan and Contrast enhanced ultrasound in people with Colorectal Cancer and Hepatic Metastases, run by University Hospital, Tours at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Hepatic Metastases
- What is being tested?
- MRI, Perfusion CT scan and Contrast enhanced ultrasound
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteFrance
- Study dates
- 1 Oct 2019to 30 Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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).
- 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
Who cannot join
- 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;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Targeted Delivery of Chemotherapy With Ultrasound and Microbubbles
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.
Read the 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.
- Conditions
- Colorectal Cancer, Hepatic Metastases
- Being tested
- MRI, Perfusion CT scan, Contrast enhanced ultrasound, Sonoporation
- Keywords
- microbubbles, sonoporation, hepatic metastases of colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIRadiation
Magnetic Resonance Imaging
Perfusion CT scanRadiation
Perfusion Computerized tomography scan
Contrast enhanced ultrasoundOther
Contrast enhanced ultrasound
SonoporationDrug
Gaseous microbubbles (Sonovue) combinated with Ultrasounds
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Radiation: MRI; Radiation: Perfusion CT scan; Other: Contrast enhanced ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 months
Secondary outcomes (10)
Safety
Safety based on National Cancer Institute (NCI), Common Terminology Criteria for Adverse events (CTCAE)
Measured: Day 3, Day 17, Day 32, Day 47
Tolerance
Tolerance based on National Cancer Institute (NCI), Common Terminology Criteria for Adverse events (CTCAE)
Measured: Day 3, Day 17, Day 32, Day 47
Maximum percent reduction in tumor density on CT scan
Maximum percent reduction in tumor density (Hounsfield units) from baseline
Measured: 2 months
Maximum percent reduction in tumor density on MRI
Maximum percent reduction in tumor density from baseline
Measured: 2 months
Assessment of tumor vascularity by Perfusion CT scan
Assessment of tumor vascularity with Perfusion CT scan
Measured: 2 months
Assessment of tumor vascularity by MRI
Assessment of tumor vascularity with MRI
Measured: 2 months
Assessment of tumor vascularity by Dynamic Contrast-Enhanced US (DCE-US)
Assessment of tumor vascularity with Dynamic Contrast-Enhanced US (DCE-US)
Measured: 2 months
Dosage of antibody anti-VEGF or anti-EGFR
Measures of serum concentration of antibody anti-VEGF or anti-EGFR
Measured: Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Dosage of antibody anti-VEGF or anti-EGFR by ELISA test
Pharmacokinetic of antibody anti-VEGF or anti-EGFR
Measured: Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Dosage of cytokines
Dosage of cytokines
Measured: Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2018
- Study start1 Oct 2019
- Primary completion30 Sep 2022
- Study completion30 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03458975
- Sponsor's protocol ID
- PRTK15-TL/SONCHIMIO
- Acronym
- SONCHIMIO
- Status last verified
- Jan 2023
- First submitted
- 2 Mar 2018
- Last updated
- 9 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Delivery of Chemotherapy With Ultrasound and Microbubbles
- ClinicalTrials.gov ID
- NCT03458975
- Acronym / sponsor ID
- SONCHIMIO / PRTK15-TL/SONCHIMIO
- Conditions
- Colorectal Cancer, Hepatic Metastases
- Keywords
- microbubbles, sonoporation, hepatic metastases of colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 8 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Selected liver metastases of the patient | Active comparator | Radiation: MRI, Radiation: Perfusion CT scan, Other: Contrast enhanced ultrasound, Drug: SonoporationLiver metastases randomized to receive sonoporation (US waves + gaseous microbubbles). The patient continue to receive the usual systemic chemotherapy |
| Not-selected liver metastases of the patient | Placebo comparator | Radiation: MRI, Radiation: Perfusion CT scan, Other: Contrast enhanced ultrasoundLiver metatstases not randomized to receive sonoporation (US waves + gaseous microbubbles). The patient continue to receive the usual systemic chemotherapy like the active comparator arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIMagnetic Resonance Imaging | Radiation | Not-selected liver metastases of the patient, Selected liver metastases of the patient |
| Perfusion CT scanPerfusion Computerized tomography scan | Radiation | Not-selected liver metastases of the patient, Selected liver metastases of the patient |
| Contrast enhanced ultrasoundContrast enhanced ultrasound | Other | Not-selected liver metastases of the patient, Selected liver metastases of the patient |
| SonoporationGaseous microbubbles (Sonovue) combinated with Ultrasounds | Drug | Selected liver metastases of the patient |
Primary outcome
Objective response for liver metastases
Time frame: 2 months
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
10 secondary outcomes
Safety
Time frame: Day 3, Day 17, Day 32, Day 47
Tolerance
Time frame: Day 3, Day 17, Day 32, Day 47
Maximum percent reduction in tumor density on CT scan
Time frame: 2 months
Maximum percent reduction in tumor density on MRI
Time frame: 2 months
Assessment of tumor vascularity by Perfusion CT scan
Time frame: 2 months
Assessment of tumor vascularity by MRI
Time frame: 2 months
Assessment of tumor vascularity by Dynamic Contrast-Enhanced US (DCE-US)
Time frame: 2 months
Dosage of antibody anti-VEGF or anti-EGFR
Time frame: Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Dosage of antibody anti-VEGF or anti-EGFR by ELISA test
Time frame: Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Dosage of cytokines
Time frame: Day1, Day 3, Day 15, Day 17, Day 32, Day 45
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MRI, Perfusion CT scan and Contrast enhanced ultrasound in people with Colorectal Cancer and Hepatic Metastases, run by University Hospital, Tours at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response for liver metastases (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2023.