Clinical trial NCT04101292: Endoscopic Optical Imaging for Precision Oncology Treatment Applied to Colorectal Tumours (Elios-Color-on-Specimen)
Official title: Endoscopic Optical Imaging for Precision Oncology Treatment Applied to Colorectal Tumours
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Colorectal Cancer
Keywords: Fluorescence
Antibody
Bevacizumab
IRDye800
Hyperspectral imaging
Light-CT Scanner
Tumour detection
Colorectal cancer
Lead sponsor: IHU Strasbourg
Sponsor class: OTHER
Collaborators: name: ARC Foundation for Cancer Research
First posted: 2019-09-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The Institute of Image-Guided Surgery (IHU) of Strasbourg is a translational research Institute aiming to develop hybrid surgery techniques. The IHU-SPECTRA research unit, entirely dedicated to the development of fluorescence-guided surgery, was set up to test several innovations as part of a large-scale project (ELIOS: Endoscopic Luminescent Imaging for Precision Oncology Surgery), funded by the ARC Foundation for Cancer Research. The proposed research protocol is part of the ELIOS project and targets in particular colon tumours.

The Holy Grail in oncology surgery is the radical removal of cancer cells in order to reduce the rate of tumour recurrences and increase the tumour's free survival.

The administration of a tumour-specific antibody, which fluoresces in the Near-Infrared ranges and which could be univocally recognized at a tumour cellular level, could provide a rapid and accurate evaluation of radical tumour removal.

The University Medical Center Groningen (UMCG) has developed a fluorescent tracer coupling Bevacizumab (which targets the Vascular Endothelial Growth Factor = VEGF) with a fluorescent dye, the IRDye800. The initial human results are very promising and no adverse events linked to the fluorescent molecule have been reported.

In parallel, an alternative optical technique that does not require the use of a fluorophore, the Hyperspectral Imaging (HSI), is a relatively new method used in image-guided and precision surgery. The company Diaspective Vision GmbH (Pepelw, Germany) produces a HSI camera, the TIVITA system, enabling to obtain spectral information from the tissues. The main advantage of HSI over fluorescence imaging is in that it is a contrast-free imaging and intrinsically quantitative although it does not provide real-time videos.

Another innovative optical imaging technology available at the IHU is FF-OCT (Light-CT Scanner, LLTechSAS, Paris, France) which allows non-destructive and high-resolution optical biopsy without tissue treatment.

The working hypothesis is that molecular fluorescence enhanced-reality allows greater precision in the differentiation of tumour tissue and healthy tissue in patients with colorectal cancer compared to the immunohistochemistry conventionally used in anatomopathology.

In parallel, this technique will be compared to hyperspectral imaging (HSI TIVITA system) and optical imaging (FF-OCT system), two potentially advantageous methods for the detection of tumour tissue.

Detailed description: The Institute of Image-Guided Surgery (IHU) of Strasbourg is a translational research Institute aiming to develop hybrid surgery techniques, less invasive and image-guided to improve the therapeutic results, in the emerging context of the precision medicine.

One of those expanding technique is fluorescence imaging that can guide the surgical procedure very accurately.

The IHU-SPECTRA research unit, entirely dedicated to the development of fluorescence-guided surgery, was set up at the IHU Strasbourg. Currently represented by a network of scientists from different fields and by industrial and academic partners in France and abroad, its short-term goals are mainly the implementation and evaluation in current clinical practice of the techniques already developed. In the long term, it is planned to test several innovations as part of a large-scale project (ELIOS: Endoscopic Luminescent Imaging for Precision Oncology Surgery), funded by the ARC Foundation for Cancer Research.

The proposed research protocol is part of the ELIOS project and targets in particular colon tumours.

The Holy Grail in oncology surgery is the radical removal of cancer cells in order to reduce the rate of tumour recurrences and increase the tumour's free survival. Tumour involvement at the resection margins is the most important predictor of tumour recurrence, leading to high recurrence rate.

However, surgery and other minimally-invasive ablative procedures are currently limited by 1) the need of wide removal of healthy tissue in order to ensure negative margins (which might lead to functional deficits and increases the risks of complications) and 2) frozen sections analysis to verify the surgical margins. They are time consuming and require considerable human resources.

The administration of a tumour-specific antibody, which fluoresces in the Near-Infrared ranges and which could be univocally recognized at a tumour cellular level, could provide a rapid and accurate evaluation of radical tumour removal. In the context of precision surgery, the development of tumour-specific fluorescent probes has made remarkable advances over recent years, with promising pre-clinical proofs of the concept, allowing for the enhanced identification of tumour residuals and metastatic lymph nodes. Recently, in a pioneer paper published on Nature, the first human case of tumour-specific fluorescence-guided surgery has been reported. Authors could remove effectively 34 intra-peritoneal implants of ovarian cancer metastasis, which were completely invisible at the naked eye. This impressive proof of the concept highlights clearly the potential impact of intraoperative tumour-specific molecular fluorescence imaging.

There is an increasing number of targeted probes which are being developed to visualize cancer cells, enabling early stage cancer detection and precise tumour resection. Particularly interesting is the strategy of coupling a fluorescent dye (IRDye800CW) with the humanized monoclonal antibodies, currently used in anticancer therapy.

The University Medical Center Groningen (UMCG), which is a strong partner of the IHU-SPECTRA unit, has developed a fluorescent tracer coupling Bevacizumab (which targets the Vascular Endothelial Growth Factor = VEGF) with the IRDye800.

The initial human results obtained together with the company Surgvision (Groningue, Pays-Bas) are very promising and have reported no adverse events linked to the fluorescent.

Bevacizumab-IRDye800CW can be either intravenously perfused or locally applied, the local application being more efficient than the perfusion.

In parallel, an alternative optical technique that does not require the use of a fluorophore will be tested. This technology, the Hyperspectral Imaging (HSI), is a relatively new method used in image-guided and precision surgery, which has shown promising results for recognition/characterization of tissues/tumours, and comprehensive assessment of physiologic tissue parameters, such as perfusion, oxygenation, and water content. Hence, it has been applied predominantly in wound imaging and -management in plastic surgery transplants, vascular surgery, chronical wounds and burn injuries.

The HSI system from a German start-up (Diaspective Vision GmbH, Pepelw, Germany) has been acquired. The company produces a HSI camera, the TIVITA system, enabling to obtain spectral information from the tissues. The only limitation, when applied to minimally-invasive surgery, is in that the TIVITA provides pictures and not real-time videos.

The main advantage of HSI over fluorescence imaging is in that it is a contrast-free imaging and intrinsically quantitative. Those characteristics make of the HSI a very promising tool in image-guided surgery, and open several windows of opportunity in terms of research programs towards miniaturization and optimization of the image-flow and artificial intelligence (AI) algorithms of tissue recognition.

Another innovative optical imaging technology available at the IHU is FF-OCT (Light-CT Scanner, LLTechSAS, Paris, France). This technology allows non-destructive and high-resolution optical biopsy without tissue treatment. The images are generated by measuring the backscattered light produced by the interaction between light and tissues of different indices. This technology has already shown its significant potential in oncology, particularly for ovarian, brain, mammary and pancreatic tissues. If validated, it could in the future complement or even replace traditional pathology, since it provides high-resolution images in a short time, without the need for treatment or staining.

The working hypothesis is that molecular fluorescence enhanced-reality allows greater precision in the differentiation of tumour tissue and healthy tissue in patients with colorectal cancer compared to the immunohistochemistry conventionally used in anatomopathology.

In parallel, this technique will be compared to hyperspectral imaging (HSI TIVITA system) and optical imaging (FF-OCT system), two potentially more advantageous methods for the detection of tumour tissue.

Eligibility criteria: Inclusion Criteria:

1. Man or woman over 18 years old
2. Patient with colorectal cancer
3. Patient able to receive and understand information related to the study and to give written informed consent.
4. Patient affiliated to the French social security system

Exclusion Criteria:

1. Pregnant or lactating patient
2. Patient in exclusion period (determined by a previous or a current study)
3. Patient under guardianship or trusteeship
4. Patient under the protection of justice

Primary outcomes:
measure: Evaluation of the sensitivity of Bevacizumab-IRDye800 to visualize tumour tissue relative to surrounding healthy tissue by the means of fluorescence intensity measurements
timeFrame: 1 day
measure: Evaluation of the sensitivity of Bevacizumab-IRDye800 to visualize tumour tissue compared to anti-VEGF antibodies by the means of fluorescence intensity measurements
timeFrame: 1 day
Secondary outcomes:
measure: Ability of Hyperspectral Imaging (HSI) to detect the tumour area on the serosal side before marking the margins of resection by the means of spectral signature characterization
timeFrame: 1 day
measure: Ability of HSI to detect the tumour area on the serosal side after marking the margins of resection by the means of spectral signature characterization
timeFrame: 1 day
measure: Ability of HSI to determine the tumour stage from the serosal side
timeFrame: 1 day
measure: HSI's ability to identify the tumoural and healthy tissue from the mucosal side compared to the results provided by histopathology and immunohistochemistry (IHC).
timeFrame: 1 day
measure: Level of accuracy of resection of a fluorescence-guided tumour determined by the presence or absence of tumourous cells on resection margins by histological examination
timeFrame: 1 day
measure: Level of accuracy of fluorescence microscopy compared to ImmunoHistoChemistry
timeFrame: 1 day
measure: Level of accuracy of Full-field optical coherence tomography (FF-OCT) by the means of a qualitative analysis
timeFrame: 1 day
Other outcomes:
Locations:
Study officials:
affiliation: Service Chirurgie Digestive et Endocrinienne, Nouvel Hôpital Civil de Strasbourg
name: Didier Mutter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: IHU Strasbourg
name: Michele DIANA, MD
role: STUDY_DIRECTOR
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