Colorectal CancerNCT04101292
Endoscopic Optical Imaging for Precision Oncology Treatment Applied to Colorectal Tumours (Elios-Color-on-Specimen)
A study testing Characterization of tumor tissue by fluorescence in people with Colorectal Cancer, run by IHU Strasbourg.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Characterization of tumor tissue by fluorescence
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2021to Jun 2023
- Phase
- Interventional
- 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
- Man or woman over 18 years old
- Patient with colorectal cancer
- Patient able to receive and understand information related to the study and to give written informed consent.
- Patient affiliated to the French social security system
Who cannot join
- Pregnant or lactating patient
- Patient in exclusion period (determined by a previous or a current study)
- Patient under guardianship or trusteeship
- Patient under the protection of justice
About this study
Official title: Endoscopic Optical Imaging for Precision Oncology Treatment Applied to Colorectal Tumours
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.
Read more
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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- Characterization of tumor tissue by fluorescence
- Keywords
- Fluorescence, Antibody, Bevacizumab, IRDye800, Hyperspectral imaging, Light-CT Scanner, Tumour detection, 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.
Characterization of tumor tissue by fluorescenceOther
- HSI Imaging of the resected specimen, from the serum and the mucous side
- FF-OCT imaging of the tumor and the healthy tissue biopsies
- Local application of Bevacizumab-IRDye800CW and visualization with the Surgvision Explorer system
- Standard anti-VEGF Immunohistochemistry and pathology
| Study group | Role | What they receive |
|---|---|---|
| Fluorescence characterization | Experimental | Not described Receives: Other: Characterization of tumor tissue by fluorescence |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the sensitivity of Bevacizumab-IRDye800 to visualize tumour tissue relative to surrounding healthy tissue by the means of fluorescence intensity measurements
Correlation between the fluorescence signal intensity of Bevacizumab-IRDye800CW emitted by tumours and sensed by near-infrared imaging systems compared to the fluorescence emitted by healthy tissue
Measured: 1 day
Evaluation of the sensitivity of Bevacizumab-IRDye800 to visualize tumour tissue compared to anti-VEGF antibodies by the means of fluorescence intensity measurements
Correlation between the fluorescence signal intensity of Bevacizumab-IRDye800CW emitted by tumours and sensed by near-infrared imaging systems compared to VEGF expression levels in immunohistochemistry and histological diagnosis
Measured: 1 day
Secondary outcomes (7)
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
Correlation of the spectral signatures between healthy and tumour bearing segments from the serosa side, obtained by HSI before marking the margins of resection
Measured: 1 day
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
Correlation of the spectral signatures between healthy and tumour bearing segments from the serosa side, obtained by HSI after marking the margins of resection
Measured: 1 day
Ability of HSI to determine the tumour stage from the serosal side
Correlation of the tumour stage specific spectral features obtained from the serosal side with the final histopathological tumour stage
Measured: 1 day
HSI's ability to identify the tumoural and healthy tissue from the mucosal side compared to the results provided by histopathology and immunohistochemistry (IHC).
Determination of the presence or absence of spectral signature obtained by HSI on two regions of interest (one located in the tumour and the other outside the tumour) and correlation with standard pathology and IHC
Measured: 1 day
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
Evaluation of the efficiency of fluorescence-guided full-thickness resection by histopathologically evaluating the presence or absence of tumours on resection margins
Measured: 1 day
Level of accuracy of fluorescence microscopy compared to ImmunoHistoChemistry
Comparison of the fluorescence signal intensity detected within and outside the tumour by fluorescence microscopy and immunohistochemical analysis
Measured: 1 day
Level of accuracy of Full-field optical coherence tomography (FF-OCT) by the means of a qualitative analysis
Qualitative analysis with FF-OCT of untreated biopsies compared to frozen sections and standard pathology
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start1 Apr 2021
- Primary completionApr 2023 (estimated)
- Study completionJun 2023 (estimated)
Why it stopped: Problems with the provision of equipment encountered during the study could not be resolved, making it impossible to take the images planned for the main objective of the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- IHU Strasbourg
- Sponsor type
- University, hospital or other
- Collaborators
- ARC Foundation for Cancer Research
- Responsible party
- Sponsor
- Investigators
- Didier Mutter, MD, PhD, Principal investigator, Service Chirurgie Digestive et Endocrinienne, Nouvel Hôpital Civil de StrasbourgMichele DIANA, MD, Study director, IHU Strasbourg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04101292
- Sponsor's protocol ID
- 19-004
- Status last verified
- Mar 2022
- First submitted
- 19 Sep 2019
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Harlaar NJ, Koller M, de Jongh SJ, van Leeuwen BL, Hemmer PH, Kruijff S, van Ginkel RJ, Been LB, de Jong JS, Kats-Ugurlu G, Linssen MD, Jorritsma-Smit A, van Oosten M, Nagengast WB, Ntziachristos V, van Dam GM. Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: a single-centre feasibility study. Lancet Gastroenterol Hepatol. 2016 Dec;1(4):283-290. doi: 10.1016/S2468-1253(16)30082-6. Epub 2016 Sep 17.
PubMed 28404198Diana M. Enabling precision digestive surgery with fluorescence imaging. Transl Gastroenterol Hepatol. 2017 Nov 21;2:97. doi: 10.21037/tgh.2017.11.06. eCollection 2017. No abstract available.
PubMed 29264435Lamberts LE, Koch M, de Jong JS, Adams ALL, Glatz J, Kranendonk MEG, Terwisscha van Scheltinga AGT, Jansen L, de Vries J, Lub-de Hooge MN, Schroder CP, Jorritsma-Smit A, Linssen MD, de Boer E, van der Vegt B, Nagengast WB, Elias SG, Oliveira S, Witkamp AJ, Mali WPTM, Van der Wall E, van Diest PJ, de Vries EGE, Ntziachristos V, van Dam GM. Tumor-Specific Uptake of Fluorescent Bevacizumab-IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study. Clin Cancer Res. 2017 Jun 1;23(11):2730-2741. doi: 10.1158/1078-0432.CCR-16-0437. Epub 2016 Nov 9.
PubMed 28119364Tjalma JJ, Garcia-Allende PB, Hartmans E, Terwisscha van Scheltinga AG, Boersma-van Ek W, Glatz J, Koch M, van Herwaarden YJ, Bisseling TM, Nagtegaal ID, Timmer-Bosscha H, Koornstra JJ, Karrenbeld A, Kleibeuker JH, van Dam GM, Ntziachristos V, Nagengast WB. Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection. J Nucl Med. 2016 Mar;57(3):480-5. doi: 10.2967/jnumed.115.166975. Epub 2015 Dec 17.
PubMed 26678613Rosenthal EL, Warram JM, de Boer E, Basilion JP, Biel MA, Bogyo M, Bouvet M, Brigman BE, Colson YL, DeMeester SR, Gurtner GC, Ishizawa T, Jacobs PM, Keereweer S, Liao JC, Nguyen QT, Olson JM, Paulsen KD, Rieves D, Sumer BD, Tweedle MF, Vahrmeijer AL, Weichert JP, Wilson BC, Zenn MR, Zinn KR, van Dam GM. Successful Translation of Fluorescence Navigation During Oncologic Surgery: A Consensus Report. J Nucl Med. 2016 Jan;57(1):144-50. doi: 10.2967/jnumed.115.158915. Epub 2015 Oct 8.
PubMed 26449839Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
PubMed 25651787Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
PubMed 29313949Kellokumpu I, Vironen J, Kairaluoma M, Jantunen I, Kautiainen H, Nuorva K. Quality of surgical care, local recurrence, and survival in patients with low- and midrectal cancers following multimodal therapy. Int J Colorectal Dis. 2012 Jan;27(1):111-20. doi: 10.1007/s00384-011-1322-5. Epub 2011 Oct 26.
PubMed 22038306Metildi CA, Felsen CN, Savariar EN, Nguyen QT, Kaushal S, Hoffman RM, Tsien RY, Bouvet M. Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Ann Surg Oncol. 2015;22(6):2082-7. doi: 10.1245/s10434-014-4144-1. Epub 2014 Oct 16.
PubMed 25319581Metildi CA, Kaushal S, Luiken GA, Hoffman RM, Bouvet M. Advantages of fluorescence-guided laparoscopic surgery of pancreatic cancer labeled with fluorescent anti-carcinoembryonic antigen antibodies in an orthotopic mouse model. J Am Coll Surg. 2014 Jul;219(1):132-41. doi: 10.1016/j.jamcollsurg.2014.02.021. Epub 2014 Mar 2.
PubMed 24768506Metildi CA, Kaushal S, Pu M, Messer KA, Luiken GA, Moossa AR, Hoffman RM, Bouvet M. Fluorescence-guided surgery with a fluorophore-conjugated antibody to carcinoembryonic antigen (CEA), that highlights the tumor, improves surgical resection and increases survival in orthotopic mouse models of human pancreatic cancer. Ann Surg Oncol. 2014 Apr;21(4):1405-11. doi: 10.1245/s10434-014-3495-y. Epub 2014 Feb 6.
PubMed 24499827Metildi CA, Tang CM, Kaushal S, Leonard SY, Magistri P, Tran Cao HS, Hoffman RM, Bouvet M, Sicklick JK. In vivo fluorescence imaging of gastrointestinal stromal tumors using fluorophore-conjugated anti-KIT antibody. Ann Surg Oncol. 2013 Dec;20 Suppl 3(0 3):S693-700. doi: 10.1245/s10434-013-3172-6. Epub 2013 Aug 14.
PubMed 23943029Tran Cao HS, Kaushal S, Metildi CA, Menen RS, Lee C, Snyder CS, Messer K, Pu M, Luiken GA, Talamini MA, Hoffman RM, Bouvet M. Tumor-specific fluorescence antibody imaging enables accurate staging laparoscopy in an orthotopic model of pancreatic cancer. Hepatogastroenterology. 2012 Sep;59(118):1994-9. doi: 10.5754/hge11836.
PubMed 22369743van Dam GM, Themelis G, Crane LM, Harlaar NJ, Pleijhuis RG, Kelder W, Sarantopoulos A, de Jong JS, Arts HJ, van der Zee AG, Bart J, Low PS, Ntziachristos V. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-alpha targeting: first in-human results. Nat Med. 2011 Sep 18;17(10):1315-9. doi: 10.1038/nm.2472.
PubMed 21926976McElroy M, Kaushal S, Luiken GA, Talamini MA, Moossa AR, Hoffman RM, Bouvet M. Imaging of primary and metastatic pancreatic cancer using a fluorophore-conjugated anti-CA19-9 antibody for surgical navigation. World J Surg. 2008 Jun;32(6):1057-66. doi: 10.1007/s00268-007-9452-1.
PubMed 18264829
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endoscopic Optical Imaging for Precision Oncology Treatment Applied to Colorectal Tumours
- ClinicalTrials.gov ID
- NCT04101292
- Acronym / sponsor ID
- 19-004
- Conditions
- Colorectal Cancer
- Keywords
- Fluorescence, Antibody, Bevacizumab, IRDye800, Hyperspectral imaging, Light-CT Scanner, Tumour detection, Colorectal cancer
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Problems with the provision of equipment encountered during the study could not be resolved, making it impossible to take the images planned for the main objective of the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- IHU StrasbourgUniversity, hospital or other
- Collaborators
- ARC Foundation for Cancer Research
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 24 Sep 2019 (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 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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fluorescence characterization | Experimental | Other: Characterization of tumor tissue by fluorescence |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Man or woman over 18 years old
- Patient with colorectal cancer
- Patient able to receive and understand information related to the study and to give written informed consent.
- Patient affiliated to the French social security system
Key exclusion criteria (4 listed)
- Pregnant or lactating patient
- Patient in exclusion period (determined by a previous or a current study)
- Patient under guardianship or trusteeship
- Patient under the protection of justice
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 |
|---|---|---|
| Characterization of tumor tissue by fluorescence* HSI Imaging of the resected specimen, from the serum and the mucous side * FF-OCT imaging of the tumor and the healthy tissue biopsies * Local application of Bevacizumab-IRDye800CW and visualization with the Surgvision Explorer system * Standard anti-VEGF Immunohistochemistry and pathology | Other | Fluorescence characterization |
Primary outcome
Evaluation of the sensitivity of Bevacizumab-IRDye800 to visualize tumour tissue relative to surrounding healthy tissue by the means of fluorescence intensity measurements
Time frame: 1 day
Correlation between the fluorescence signal intensity of Bevacizumab-IRDye800CW emitted by tumours and sensed by near-infrared imaging systems compared to the fluorescence emitted by healthy tissue
Evaluation of the sensitivity of Bevacizumab-IRDye800 to visualize tumour tissue compared to anti-VEGF antibodies by the means of fluorescence intensity measurements
Time frame: 1 day
Correlation between the fluorescence signal intensity of Bevacizumab-IRDye800CW emitted by tumours and sensed by near-infrared imaging systems compared to VEGF expression levels in immunohistochemistry and histological diagnosis
7 secondary outcomes
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
Time frame: 1 day
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
Time frame: 1 day
Ability of HSI to determine the tumour stage from the serosal side
Time frame: 1 day
HSI's ability to identify the tumoural and healthy tissue from the mucosal side compared to the results provided by histopathology and immunohistochemistry (IHC).
Time frame: 1 day
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
Time frame: 1 day
Level of accuracy of fluorescence microscopy compared to ImmunoHistoChemistry
Time frame: 1 day
Level of accuracy of Full-field optical coherence tomography (FF-OCT) by the means of a qualitative analysis
Time frame: 1 day
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Background: PubMed 28404198Harlaar NJ, Koller M, de Jongh SJ, van Leeuwen BL, Hemmer PH, Kruijff S, van Ginkel RJ, Been LB, de Jong JS, Kats-Ugurlu G, Linssen MD, Jorritsma-Smit A, van Oosten M, Nagengast WB, Ntziachristos V, van Dam GM. Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: a single-centre feasibility study. Lancet Gastroenterol Hepatol. 2016 Dec;1(4):283-290. doi: 10.1016/S2468-1253(16)30082-6. Epub 2016 Sep 17.
- Background: PubMed 29264435Diana M. Enabling precision digestive surgery with fluorescence imaging. Transl Gastroenterol Hepatol. 2017 Nov 21;2:97. doi: 10.21037/tgh.2017.11.06. eCollection 2017. No abstract available.
- Background: PubMed 28119364Lamberts LE, Koch M, de Jong JS, Adams ALL, Glatz J, Kranendonk MEG, Terwisscha van Scheltinga AGT, Jansen L, de Vries J, Lub-de Hooge MN, Schroder CP, Jorritsma-Smit A, Linssen MD, de Boer E, van der Vegt B, Nagengast WB, Elias SG, Oliveira S, Witkamp AJ, Mali WPTM, Van der Wall E, van Diest PJ, de Vries EGE, Ntziachristos V, van Dam GM. Tumor-Specific Uptake of Fluorescent Bevacizumab-IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study. Clin Cancer Res. 2017 Jun 1;23(11):2730-2741. doi: 10.1158/1078-0432.CCR-16-0437. Epub 2016 Nov 9.
- Background: PubMed 26678613Tjalma JJ, Garcia-Allende PB, Hartmans E, Terwisscha van Scheltinga AG, Boersma-van Ek W, Glatz J, Koch M, van Herwaarden YJ, Bisseling TM, Nagtegaal ID, Timmer-Bosscha H, Koornstra JJ, Karrenbeld A, Kleibeuker JH, van Dam GM, Ntziachristos V, Nagengast WB. Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection. J Nucl Med. 2016 Mar;57(3):480-5. doi: 10.2967/jnumed.115.166975. Epub 2015 Dec 17.
- Background: PubMed 26449839Rosenthal EL, Warram JM, de Boer E, Basilion JP, Biel MA, Bogyo M, Bouvet M, Brigman BE, Colson YL, DeMeester SR, Gurtner GC, Ishizawa T, Jacobs PM, Keereweer S, Liao JC, Nguyen QT, Olson JM, Paulsen KD, Rieves D, Sumer BD, Tweedle MF, Vahrmeijer AL, Weichert JP, Wilson BC, Zenn MR, Zinn KR, van Dam GM. Successful Translation of Fluorescence Navigation During Oncologic Surgery: A Consensus Report. J Nucl Med. 2016 Jan;57(1):144-50. doi: 10.2967/jnumed.115.158915. Epub 2015 Oct 8.
- Background: PubMed 25651787Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. Epub 2015 Feb 4.
- Background: PubMed 29313949Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
- Background: PubMed 22038306Kellokumpu I, Vironen J, Kairaluoma M, Jantunen I, Kautiainen H, Nuorva K. Quality of surgical care, local recurrence, and survival in patients with low- and midrectal cancers following multimodal therapy. Int J Colorectal Dis. 2012 Jan;27(1):111-20. doi: 10.1007/s00384-011-1322-5. Epub 2011 Oct 26.
- Background: PubMed 25319581Metildi CA, Felsen CN, Savariar EN, Nguyen QT, Kaushal S, Hoffman RM, Tsien RY, Bouvet M. Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Ann Surg Oncol. 2015;22(6):2082-7. doi: 10.1245/s10434-014-4144-1. Epub 2014 Oct 16.
- Background: PubMed 24768506Metildi CA, Kaushal S, Luiken GA, Hoffman RM, Bouvet M. Advantages of fluorescence-guided laparoscopic surgery of pancreatic cancer labeled with fluorescent anti-carcinoembryonic antigen antibodies in an orthotopic mouse model. J Am Coll Surg. 2014 Jul;219(1):132-41. doi: 10.1016/j.jamcollsurg.2014.02.021. Epub 2014 Mar 2.
- Background: PubMed 24499827Metildi CA, Kaushal S, Pu M, Messer KA, Luiken GA, Moossa AR, Hoffman RM, Bouvet M. Fluorescence-guided surgery with a fluorophore-conjugated antibody to carcinoembryonic antigen (CEA), that highlights the tumor, improves surgical resection and increases survival in orthotopic mouse models of human pancreatic cancer. Ann Surg Oncol. 2014 Apr;21(4):1405-11. doi: 10.1245/s10434-014-3495-y. Epub 2014 Feb 6.
- Background: PubMed 23943029Metildi CA, Tang CM, Kaushal S, Leonard SY, Magistri P, Tran Cao HS, Hoffman RM, Bouvet M, Sicklick JK. In vivo fluorescence imaging of gastrointestinal stromal tumors using fluorophore-conjugated anti-KIT antibody. Ann Surg Oncol. 2013 Dec;20 Suppl 3(0 3):S693-700. doi: 10.1245/s10434-013-3172-6. Epub 2013 Aug 14.
- 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.
Didier Mutter, MD, PhD principal investigator
Service Chirurgie Digestive et Endocrinienne, Nouvel Hôpital Civil de Strasbourg
Michele DIANA, MD study director
IHU Strasbourg
Questions about this trial
What is this clinical trial studying?
A study testing Characterization of tumor tissue by fluorescence in people with Colorectal Cancer, run by IHU Strasbourg.
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 4 inclusion and 4 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: withdrawn, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Evaluation of the sensitivity of Bevacizumab-IRDye800 to visualize tumour tissue relative to surrounding healthy tissue by the means of fluorescence intensity measurements (time frame: 1 day). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04101292, which also lists 24 linked publications.
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 17 Apr 2026.