Clinical Evaluation Of Needle-based Confocal Laser Endomicroscopy in The Lymph Nodes Along With Masses and Cystic Tumors of the Pancreas (CONTACT)

• ClinicalTrials.gov Identifier: NCT01563133
• Recruitment Status: Unknown
• First Posted: March 26, 2012
• Last Update Posted: August 29, 2017
• Sponsor: Mauna Kea Technologies
• Information provided by (Responsible Party): Mauna Kea Technologies

Study Description

Brief Summary:

This study focuses on three different lesions: pancreatic cysts, lymph nodes near the gastrointestinal tract and pancreatic masses.

On one hand, the results obtained during previous studies are more advanced for the assessment of the diagnostic performance of Cellvizio needle-based Confocal Laser Endomicroscopy (nCLE) system for Pancreatic cysts. Safety and technical feasibility have already been performed, and an interpretation criteria classification exists. On the other hand, results for pancreatic masses and Lymph nodes are less developed.

The study therefore comprises two sub-studies, one on the pancreatic cysts, and another on pancreatic masses and lymph nodes.

1. Cysts The primary hypothesis of the study is that using nCLE in addition to EUS-FNA and tissue sampling allows better characterization of pancreatic cysts and improves appropriate therapeutic decision-making.

   For physicians, integrating nCLE into the diagnostic algorithm of pancreatic cysts could impact patient management by :

   • Ruling out malignancy for patients with benign appearing nCLE images.
   • Characterizing more malignant tumors in the pancreas.
2. Pancreatic masses and Lymph nodes The primary hypothesis of the study is that in vivo imaging of lymph-nodes near the gastrointestinal tract and pancreatic masses during EUS-FNA procedures is feasible and that descriptive criteria can be defined to further differentiate the different types of lesions.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cyst; Pancreatic Neoplasms; Pancreatic Adenoma; Pancreatic Cancer; Pancreatic Islet Cell Tumors; Lymph Node; Lymphadenopathy	Procedure: EUS-FNA; Device: nCLE	Not Applicable

Detailed Description:

1. Medical background Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. This disease is associated with a high mortality rate: the 5-year survival rate is estimated to be 4%. This is mainly due to the fact that the disease is often discovered at an already advanced disease state, which carries a dismal prognosis.

   1.1. Pancreatic Cysts

   Pancreatic cysts are quite rare, but are being increasingly recognized due to the expanding use of cross-sectional imaging. They are classified into three main classes:

   • Pseudocysts
   • Serous cysts : either serous cystic neoplasms (SCN) or Solid pseudo-papillary neoplasm (SPN)
   • Mucinous cystic neoplasms : either Intraductal Papillary Mucinous Neoplasm (IPMN) or mucinous cystadenomas/mucinous cystadenocarcinoma(MCN) Mucinous cystic neoplasms are considered to be malignant or pre-malignant and are considered for surgical resection, whereas pseudocysts and serous cysts are considered benign and with a low potential for malignancy. Pseudocysts and serous cysts are usually only considered for surgical resection when symptomatic or enlarging.

   1.2. Pancreatic masses Pancreatic solid masses can be either exocrine or endocrine tumors, or metastatic.Exocrine tumors are by far the most common type of pancreas cancer. Most of them are malignant. About 96% of cancers of the exocrine pancreas are adenocarcinomas, which is the most aggressive form of pancreas cancer.Endocrine tumors are uncommon. They represent 4% of pancreas tumors. They are known as neuroendocrine tumors (NETs), or islet cell tumors. These tumors can be benign or malignant.

   1.3. Lymph nodes Lymph nodes are examined in a patient with a suspicion of, or confirmed, cancer, as part of the staging. They may be either normal, inflammatory, or malignant.

2. Clinical background

   2.1. EUSFNA Endoscopic Ultrasound (EUS) is the diagnostic method of choice when a pancreatic lesion is found incidentally on cross-sectional imaging. Endoscopic UltraSound-guided Fine Needle Aspiration (EUS FNA) (respectively Endobronchial Ultrasound-guided Fine Needle Aspiration (EBUS FNA)) are procedures where a target tissue in proximity to the GI tract (respectively the pulmonary tract) is biopsied using a fine needle guided in real time by an ultrasound probe fixed at the tip of an endoscope.It may therefore be applied to pancreatic lesions, or lymph nodes examination.

   2.2. nCLE The principle of needle-based Confocal Laser Endomicroscopy (nCLE) is to image organs within or adjacent to the GI or respiratory tracts with a miniprobe inserted through an endoscopic needle. The fundamental technology as well as the principle of operation of nCLE are substantially similar to pCLE.

3. Clinical evidence More than 100 patients have already underwent an nCLE procedure, in the past studies. A first feasibility study enabled to define the final type of probe which would fit into a EUSFNA needle, and the INSPECT study enabled to define interpretation criteria on the micro-structure of pancreatic cysts. Less data is available on pancreatic masses and lymph nodes, except for a few images done in the first feasibility study.

4. Objectives

   4.1. Cysts 4.1.1. The primary objective of the study is to assess the diagnostic performance of the Cellvizio nCLE system in diagnosing pancreatic cysts, when associated with other diagnostic information.

   4.1.2. The secondary objectives are to assess the potential impact of the Cellvizio nCLE system on patient management and validate the interpretation classification criteria that were created during the previous INSPECT study on cysts.

   4.2. Pancreatic masses and Lymph nodes 4.2.1. The primary objective of the study is to define criteria of nCLE sequences in lymph nodes and pancreatic masses.

   4.2.2. The secondary objectives are to evaluate feasibility and safety of the Cellvizio nCLE during EUS-FNA procedures, build an atlas of images of nCLE sequences of pancreatic masses and lymph nodes, and, finally, retrospectively assess the diagnostic performance of nCLE in the diagnosis of pancreatic masses and lymph nodes, when associated with other diagnostic information

5. Design This study will be conducted in three centers in France.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 330 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Clinical Evaluation Of NCLE in The Lymph Nodes Along With Masses and Cystic Tumors of the Pancreas
• Study Start Date: June 2012
• Actual Primary Completion Date: March 2, 2016
• Estimated Study Completion Date: March 2019

Arms and Interventions

Arm	Intervention/treatment
Lymph nodes, pancreatic masses & cysts	Procedure: EUS-FNA; Endoscopic ultrasound fine needle aspiration: ultrasound endoscopy of a lesion with aspiration of the lesion fluid through a needle; Other Names: ultrasonographic endoscopy; EUS-guided FNA; Device: nCLE; needle-based Confocal Laser Endomicroscopy

Outcome Measures

Primary Outcome Measures :

1. Diagnostic performance of the Cellvizio nCLE system in the characterization of pancreatic cysts [ Time Frame: Within 6 months after the end of Follow-up period ]
2. Descriptive criteria in nCLE sequences for the characterization of pancreatic masses and lymph nodes [ Time Frame: Within one year after the end of the follow-up period ]

Secondary Outcome Measures :

1. Impact of the Cellvizio nCLE system on the management of a patient with pancreatic cyst [ Time Frame: Within one year after the end of the follow-up period ]
2. Validation of the interpretation criteria classification for pancreatic cysts [ Time Frame: within 6 months after the end of the follow-up period ]
3. Atlas of images of nCLE sequences of pancreatic masses and lymph nodes during EUS-FNA [ Time Frame: within 3 months of the end of the follow-up period ]
4. Diagnostic performance of nCLE in the diagnosis of pancreatic masses and lymph nodes, when associated with other diagnostic information [ Time Frame: within one year after the end of the follow-up period ]
5. Feasibility and safety data on nCLE during EUS-FNA procedure [ Time Frame: Within 3 months after the end of the enrollment period ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female > 18 years of age.
• Patient indicated for a first EUS-FNA for a pancreatic cyst, lymph node or pancreatic mass, or
• Patients who had previous non-diagnostic tissue sampling taken during a previous EUS-FNA for pancreatic cyst, lymph nodes, pancreatic mass, more than three months ago.
• Patient with known pancreatic cyst or mass detected at cross-sectional imaging or suspicious lymph nodes reachable via EUSFNA
• Willing and able to comply with study procedures and provide written informed consent to participate in the study.

Add for lymph nodes:

- any lymph node reachable with EUS-FNA

Add for pancreatic mass:

• any size
• any location in the pancreas

Exclusion Criteria:

• Subjects for whom EUS-FNA procedures are contraindicated
• Known allergy to fluorescein dye
• If female, pregnant based on a positive hCG serum or an in vitro diagnostic test result or breast-feeding

Add for cysts:

• Subject with multiple cysts
• size < 20mm in diameter
• previous EUS-FNA procedure performed less than 3 months ago - Patients suffering chronic calcifying pancreatitis

Add for lymph nodes:

• size < 5mm in diameter
• If patients present several suspicious lymph nodes, only one of them will be imaged during the nCLE procedure

Add for pancreatic mass:

- If patient present several pancreatic masses, only one of them will be imaged during the nCLE procedure

Contacts and Locations

Locations

France

Hôpital Saint-Philibert

Lomme, France, 59462

Hôpital Jean Mermoz

Lyon, France, 69008

Institut Paoli Calmettes

Marseille, France, 13273

Sponsors and Collaborators

Mauna Kea Technologies

Investigators

• Principal Investigator: Marc Giovannini, MD; Institut Paoli-Calmettes

More Information

Publications:

Adsay NV. Cystic neoplasia of the pancreas: pathology and biology. J Gastrointest Surg. 2008 Mar;12(3):401-4. Epub 2007 Oct 24. Review.

Levy MJ, Clain JE. Evaluation and management of cystic pancreatic tumors: emphasis on the role of EUS FNA. Clin Gastroenterol Hepatol. 2004 Aug;2(8):639-53. Review.

Hutchins GF, Draganov PV. Cystic neoplasms of the pancreas: a diagnostic challenge. World J Gastroenterol. 2009 Jan 7;15(1):48-54. Review.

Attasaranya S, Pais S, LeBlanc J, McHenry L, Sherman S, DeWitt JM. Endoscopic ultrasound-guided fine needle aspiration and cyst fluid analysis for pancreatic cysts. JOP. 2007 Sep 7;8(5):553-63.

Becker V, Vercauteren T, von Weyhern CH, Prinz C, Schmid RM, Meining A. High-resolution miniprobe-based confocal microscopy in combination with video mosaicing (with video). Gastrointest Endosc. 2007 Nov;66(5):1001-7. Epub 2007 Sep 4.

Meining A, Saur D, Bajbouj M, Becker V, Peltier E, Höfler H, von Weyhern CH, Schmid RM, Prinz C. In vivo histopathology for detection of gastrointestinal neoplasia with a portable, confocal miniprobe: an examiner blinded analysis. Clin Gastroenterol Hepatol. 2007 Nov;5(11):1261-7. Epub 2007 Aug 6.

Kiesslich R, Gossner L, Goetz M, Dahlmann A, Vieth M, Stolte M, Hoffman A, Jung M, Nafe B, Galle PR, Neurath MF. In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol. 2006 Aug;4(8):979-87. Epub 2006 Jul 13.

Pohl H, Rösch T, Vieth M, Koch M, Becker V, Anders M, Khalifa AC, Meining A. Miniprobe confocal laser microscopy for the detection of invisible neoplasia in patients with Barrett's oesophagus. Gut. 2008 Dec;57(12):1648-53. doi: 10.1136/gut.2008.157461. Epub 2008 Aug 28.

Buchner AM, Shahid MW, Heckman MG, Krishna M, Ghabril M, Hasan M, Crook JE, Gomez V, Raimondo M, Woodward T, Wolfsen HC, Wallace MB. Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology. 2010 Mar;138(3):834-42. doi: 10.1053/j.gastro.2009.10.053. Epub 2009 Nov 10.

Meining A, Frimberger E, Becker V, Von Delius S, Von Weyhern CH, Schmid RM, Prinz C. Detection of cholangiocarcinoma in vivo using miniprobe-based confocal fluorescence microscopy. Clin Gastroenterol Hepatol. 2008 Sep;6(9):1057-60. doi: 10.1016/j.cgh.2008.04.014. Epub 2008 Jul 17.

Meining A, Phillip V, Gaa J, Prinz C, Schmid RM. Pancreaticoscopy with miniprobe-based confocal laser-scanning microscopy of an intraductal papillary mucinous neoplasm (with video). Gastrointest Endosc. 2009 May;69(6):1178-80. doi: 10.1016/j.gie.2008.06.013. Epub 2009 Jan 18.

Konda VJ, Aslanian HR, Wallace MB, Siddiqui UD, Hart J, Waxman I. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc. 2011 Nov;74(5):1049-60. doi: 10.1016/j.gie.2011.07.018. Epub 2011 Sep 15.

Giovannini M, Caillol F, Poizat F, Bories E, Pesenti C, Monges G, Raoul JL. Feasibility of Intratumoral Confocal Microscopy under Endoscopic Ultrasound Guidance. Endosc Ultrasound. 2012 Jul;1(2):80-3. doi: 10.7178/eus.02.005.

Wallace MB, Meining A, Canto MI, Fockens P, Miehlke S, Roesch T, Lightdale CJ, Pohl H, Carr-Locke D, Löhr M, Coron E, Filoche B, Giovannini M, Moreau J, Schmidt C, Kiesslich R. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther. 2010 Mar;31(5):548-52. doi: 10.1111/j.1365-2036.2009.04207.x. Epub 2009 Nov 30.

Becker V, Wallace MB, Fockens P, von Delius S, Woodward TA, Raimondo M, Voermans RP, Meining A. Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos). Gastrointest Endosc. 2010 Jun;71(7):1260-6. doi: 10.1016/j.gie.2010.01.010. Epub 2010 Apr 24.

Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol. 2007 Oct;102(10):2339-49. Epub 2007 Aug 31. Review.

Bhutani MS. Role of endoscopic ultrasonography in the diagnosis and treatment of cystic tumors of the pancreas. JOP. 2004 Jul;5(4):266-72. Review.

Sahani DV, Kadavigere R, Saokar A, Fernandez-del Castillo C, Brugge WR, Hahn PF. Cystic pancreatic lesions: a simple imaging-based classification system for guiding management. Radiographics. 2005 Nov-Dec;25(6):1471-84. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Palazzo M, Sauvanet A, Gincul R, Borbath I, Vanbiervliet G, Bourdariat R, Lemaistre AI, Pujol B, Caillol F, Palazzo L, Aubert A, Maire F, Buscail L, Giovannini M, Marque S, Napoléon B. Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions. Surg Endosc. 2019 Aug 13. doi: 10.1007/s00464-019-07062-9. [Epub ahead of print]

Napoleon B, Palazzo M, Lemaistre AI, Caillol F, Palazzo L, Aubert A, Buscail L, Maire F, Morellon BM, Pujol B, Giovannini M. Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation study in patients with definite diagnosis. Endoscopy. 2019 Sep;51(9):825-835. doi: 10.1055/a-0732-5356. Epub 2018 Oct 22.

Giovannini M, Caillol F, Monges G, Poizat F, Lemaistre AI, Pujol B, Lucidarme D, Palazzo L, Napoléon B. Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in solid pancreatic masses. Endoscopy. 2016 Oct;48(10):892-8. doi: 10.1055/s-0042-112573. Epub 2016 Aug 30.

Napoléon B, Lemaistre AI, Pujol B, Caillol F, Lucidarme D, Bourdariat R, Morellon-Mialhe B, Fumex F, Lefort C, Lepilliez V, Palazzo L, Monges G, Filoche B, Giovannini M. A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy. 2015 Jan;47(1):26-32. doi: 10.1055/s-0034-1390693. Epub 2014 Oct 17.

• Responsible Party: Mauna Kea Technologies
• ClinicalTrials.gov Identifier: NCT01563133
• Other Study ID Numbers: MKT-2012-nCLE-02
• First Posted: March 26, 2012
• Last Update Posted: August 29, 2017
• Last Verified: August 2017

Keywords provided by Mauna Kea Technologies:

endomicroscopy; needle-based; pancreatic; cyst; mass; EUSFNA

Additional relevant MeSH terms:

Pancreatic Neoplasms; Adenoma; Pancreatic Cyst; Adenoma, Islet Cell; Lymphadenopathy; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Lymphatic Diseases; Cysts; Pancrelipase; Gastrointestinal Agents