Assessment of Indocyanine Green as a Near-Infrared Fluorescent Contrast Agent for Image-guided Liver Surgery

Liver Neoplasms Clinical Trial

— HEPATOFLUO  

Official title:

Evaluation, for Patients Requiring a Liver Cancer Surgery, of the Use of Fluorescence Imaging Device: Faisability and Efficiency of Lesional and/or Anatomical Marking

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01738217
• Other study ID #: HEPATOFLUO
• Secondary ID: ET12-066
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 26, 2012
• Last updated: July 7, 2015
• Start date: April 2013
• Est. completion date: June 2015

Study information

• Verified date: July 2015
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

This is a prospective, monocentric, non-randomized, phase I-II study. The goal is to assess the faisability and the capabilities of fluorescence imaging in hepatic surgery, and specially to help the surgeon while performing liver surgery.

This study will be performed on patient intended to undergo a liver cancer surgery.It will contain three steps, assessing the following items:

• Step 1: to assess the faisability of the use of the Fluobeam, in actual clinical surgical conditions and validate the data obtained in the preclinical phase,

• Step 2: to assess the ability of the combination of ICG and Fluobeam to mark hepatic lesions,

• Step 3: to assess the ability of the combination of ICG and Fluobeam to help in guiding per-hepatectomy.

3 to 6 patients will be enrolled in the first step, 20 in the second step and 20 in the third step.

Patients will be followed during 4 weeks after the surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patient

• Affected of hepatic cancerous lesions whatever they are

• Requiring a one or two steps hepatectomy by laparotomy

• ECOG performance status (PS)= 2

• Mandatory affiliation to health security insurance

• Written informed consent

Exclusion Criteria:

• With a contraindication or hypersensitivity to ICG administration in medical history

• Having already undergone a major hepatic surgery (more than three segments) or major biliar surgery (context of major iterative hepatic surgery)

• Unable to be followed during the duration of the study, for social, family, geographical or psychological reasons

• Pregnant or breast-feeding woman (urinary strip must be negative at the time of the inclusion in the study for women in age to procreate)

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Liver Neoplasms

Intervention

Procedure:
• Fluobeam

Locations

Country	Name	City	State
France	Centre Léon Bérard	Lyon Cedex 08

Sponsors (1)

Lead Sponsor	Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

References & Publications (22)

Aoki T, Murakami M, Yasuda D, Shimizu Y, Kusano T, Matsuda K, Niiya T, Kato H, Murai N, Otsuka K, Kusano M, Kato T. Intraoperative fluorescent imaging using indocyanine green for liver mapping and cholangiography. J Hepatobiliary Pancreat Sci. 2010 Sep;17(5):590-4. doi: 10.1007/s00534-009-0197-0. Epub 2009 Oct 21. — View Citation

Aoki T, Yasuda D, Shimizu Y, Odaira M, Niiya T, Kusano T, Mitamura K, Hayashi K, Murai N, Koizumi T, Kato H, Enami Y, Miwa M, Kusano M. Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection. World J Surg. 2008 Aug;32(8):1763-7. doi: 10.1007/s00268-008-9620-y. — View Citation

Barbare JC. Quantification de la fonction hépatique: Pourquoi et comment? John Libbey Eurotext. HEPATO-GASTRO.5(6):423-431,1998.

Billingsley KG, Jarnagin WR, Fong Y, Blumgart LH. Segment-oriented hepatic resection in the management of malignant neoplasms of the liver. J Am Coll Surg. 1998 Nov;187(5):471-81. — View Citation

Gotoh K, Yamada T, Ishikawa O, Takahashi H, Eguchi H, Yano M, Ohigashi H, Tomita Y, Miyamoto Y, Imaoka S. A novel image-guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation. J Surg Oncol. 2009 Jul 1;100(1):75-9. doi: 10.1002/jso.21272. — View Citation

Hamamatsu Photonics-Pulsion Medical System.PDE Photodynamic Eye. http://www.iht-ltd.com/pde-photodynamic-eye/

Hamoui M; Marchand JP. Boutabrine H. Navarro F. L'évaluation préopératoire du risque d'insuffisance hépatocellulaire lors des résections hépatiques sur foie cirrhotique. John Libbey Eurotext.HEPATO-GASTRO. 16(1):11-19, 2009

HAS. Guide ALD-Tumeur maligne, affection maligne du tissu lymphatique ou hématopoïétique-Cancer colorectal Adénocarcinome. http://www.e-cancer.fr/soins/recommandations/cancers-digestifs

HAS.Guide ALD30-Tumeur maligne, affection maligne du tissu lymphatique ou hématopoïétique-Cancer primitif du foie. http://www.e-cancer.fr/soins/recommandations/cancers-digestifs

Ishizawa T, Fukushima N, Shibahara J, Masuda K, Tamura S, Aoki T, Hasegawa K, Beck Y, Fukayama M, Kokudo N. Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer. 2009 Jun 1;115(11):2491-504. doi: 10.1002/cncr.24291. — View Citation

Ishizuka M, Kubota K, Kita J, Shimoda M, Kato M, Sawada T. Intraoperative observation using a fluorescence imaging instrument during hepatic resection for liver metastasis from colorectal cancer. Hepatogastroenterology. 2012 Jan-Feb;59(113):90-2. doi: 10.5754/hge11223. — View Citation

Jarnagin WR, Bach AM, Winston CB, Hann LE, Heffernan N, Loumeau T, DeMatteo RP, Fong Y, Blumgart LH. What is the yield of intraoperative ultrasonography during partial hepatectomy for malignant disease? J Am Coll Surg. 2001 May;192(5):577-83. — View Citation

Morita Y, Sakaguchi T, Unno N, Shibasaki Y, Suzuki A, Fukumoto K, Inaba K, Baba S, Takehara Y, Suzuki S, Konno H. Detection of hepatocellular carcinomas with near-infrared fluorescence imaging using indocyanine green: its usefulness and limitation. Int J Clin Oncol. 2013 Apr;18(2):232-41. doi: 10.1007/s10147-011-0367-3. Epub 2011 Dec 27. — View Citation

O2View. ArteMIS Handheld Complete System. http://o2view.com/

Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, Curley SA, Loyer EM, Muratore A, Mentha G, Capussotti L, Vauthey JN. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005 May;241(5):715-22, discussion 722-4. — View Citation

Reuthebuch O, Häussler A, Genoni M, Tavakoli R, Odavic D, Kadner A, Turina M. Novadaq SPY: intraoperative quality assessment in off-pump coronary artery bypass grafting. Chest. 2004 Feb;125(2):418-24. — View Citation

Rivoire M.Diagnostiquer une tumeur du foie primitive et secondaire. http://cancero.unice.fr/sitelocal/disciplines/niveaudiscipline/cancerologie/numlecon151/leconimprim.pdf

Schaafsma BE, Mieog JS, Hutteman M, van der Vorst JR, Kuppen PJ, Löwik CW, Frangioni JV, van de Velde CJ, Vahrmeijer AL. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011 Sep 1;104(3):323-32. doi: 10.1002/jso.21943. Epub 2011 Apr 14. Review. — View Citation

Slim K, Blay JY, Brouquet A, Chatelain D, Comy M, Delpero JR, Denet C, Elias D, Fléjou JF, Fourquier P, Fuks D, Glehen O, Karoui M, Kohneh-Shahri N, Lesurtel M, Mariette C, Mauvais F, Nicolet J, Perniceni T, Piessen G, Regimbeau JM, Rouanet P, sauvanet A, — View Citation

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First step: assess the feasibility and the acceptability of Fluobeam	The ability to detect fluorescence; The ability to investigate the mobilized parenchyma; The ability to use the medical device following requested asepsis procedures; Surgeon satisfaction; Nurse satisfaction	During surgery on day 0	No
Primary	Second step: assess the rate of patients in whom, all of the lesions (superficial/deep) will be detected by means of the Fluobeam medical device in peroperative or in postoperative.		During surgery on day 0	No
Primary	Third step: assess the rate of patients in whom, among the 7 liver segments, the surgeon will be able to selectively target a predefined area.		During surgery on day 0	No
Secondary	First step: assess the ability to visualize the fluorescent anatomical areas		During surgery on day 0	No
Secondary	First step: Quantify the fluorescence	by using the images obtained during the surgery	After the surgery, on day 0	No
Secondary	First step: assess the ability to review saved data		After the surgery, on day 0	No
Secondary	Second step: assess the ability to detect tumor lesions which were not previously known.	Assessment of the number of lesions detected thanks to the medical device. The malignant aspect must be confirmed by an anatomopathological analysis.	During surgery on day 0	No
Secondary	Second step: assess the rate of modifications of the surgical plan.	Number of patients for whom the surgery would be modified after using Fluobeam.	During surgery on day 0	No
Secondary	Second step: assess the quality of the resection margins.	It will be measured using the residual fluorescence and the pathology analysis	After the surgery on day 0	No
Secondary	Second step: assess the depth limit of detection of the fluorescence.	It will be assessed after the anatomopathological analysis.	After the pathology analysis on day 0	No
Secondary	Second step: Quantify the fluorescence.	From images obtained during the surgery and from the sample analysed by a pathologist.	After the surgery, on day 0	No
Secondary	Second step: assess the number of asepsis due to Fluobeam		During surgery on day 0	No
Secondary	Third step: assess the ability to detect tumor lesions which were not previously known.	Assessment of the number of lesions detected thanks to the medical device. The malignant aspect must be confirmed by an anatomopathological analysis	During surgery on day 0	No
Secondary	Third step: quantify the fluorescence.	From images obtained during the surgery and from the sample analysed by a pathologist.	After the surgery on day 0	No
Secondary	Third step: assess the ability to administer two doses of ICG in the same patient	one before and one during the surgery (tumor detection and segment targeting respectively).	On day 0	No
Secondary	Third step: assess the number of asepsis due to Fluobeam		During surgery on day 0	No
Secondary	Third step: assess the ability of the medical device to detect tumor lesions which were previously known.	Number of lesions seen on images before and during the surgery and detected by Fluobeam.	On day 0	No