TECR & ECM Placement for Esophageal High Grade Dysplasia

NCT ID: NCT02396745

Last Updated: 2019-03-19

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-25

Study Completion Date

2018-03-22

Brief Summary

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This study will test the safety and effectiveness of esophageal transoral endoscopic circumferential resection (TECR) using an extracellular matrix (ECM) placement to treat Barrett's esophagus in patients with high-grade dysplasia (HGD). Endoscopic circumferential resection using ECM placement has been introduced as a less invasive, externally incision-less approach to treat patients with esophageal high grade dysplasia; a pre-cancerous condition. In this procedure, the entire length of diseased (abnormal) mucosa (esophagus lining) will be removed using an endoscope that will be inserted through the mouth. The ECM will be placed over the area that is being removed with a temporary, expandable stent to prevent narrowing of the esophagus. The stent is being used to hold the ECM in place as the body begins the healing process. This stent will be removed 14 days (±4 days) after this procedure. Follow-up esophagogastroduodenoscopies (EGD), barium swallow x-ray tests, and questionnaires will take place for 12 months following the procedure. The result of this study may help doctors determine if this procedure would be a more effective treatment option for HGD in the future.

Detailed Description

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This is a single-center, prospective, single arm study involving 10 patients with an established diagnosis of Barrett's Esophagus (BE) with High Grade Dysplasia (HGD). Potential subjects will be prescreened to assess eligibility and must meet inclusion criteria. In order to make this initial qualification, pathology results of biopsies and EMR collected during initial EGD will be made available to the Investigator prior to patient consent. Following informed consent and as part of routine care, all potential participants will undergo endoscopic ultrasound (EUS) and a PET/CT scan to confirm that there is no lymph node involvement or other metastatic lesions prior to the procedure. Clinical data will be collected at baseline to assess the subjects' medical status including: demographics, medical history, physical examination, vital signs, and blood testing. Cardiac and pulmonary clearance will be obtained if needed based on medical history and will include a chest x-ray, ECG, and pulmonary function test. In addition, the subjects will complete three questionnaires prior to the procedure: dysphagia severity questionnaire, SF-36, and GERD-HRQL.

At the time of the procedure, participants will undergo TECR with ECM placement using a fully covered self-expanding metal stent to temporarily hold the ECM in place. Prior to hospital discharge, a barium swallow test (BaSW) will be performed at Day 1 following the study procedure to evaluate the passage of contrast through the GEJ. If the BaSW results in suspicious findings of esophageal perforation or mucosal necrosis, an upper endoscopy will be performed for further evaluation. The first primary safety endpoint for this study will be assessed following the procedure and BaSW and before discharge from the hospital. At this time point any adverse events will be assessed and recorded.

All subjects will undergo the same follow-up procedures, including questionnaires and post-procedure EGDs performed at Week 2, Month 1, Month 3, Month 6, Month 9 and Month 12 to visually assess tissue healing, recurrent disease, and if stricture formation is present. Biopsies will be taken during follow-up EGDs so that pathology can rule out recurrence of BE and HGD. Subjects will have a barium swallow x-ray at Month 1, Month 3, Month 6, Month 9, and Month 12 to evaluate the potential presence of stricture formation.

During Week 2 EGD, the stent will be removed during the upper endoscopy. If at any time point a subject has dysphagia with stricture formation (30% reduction in esophageal luminal diameter), routine dilation using a balloon catheter will be performed during the EGD. Validated questionnaires including dysphagia severity questionnaire, SF-36 and GERD-HRQL will be administered to objectively assess the severity of symptoms and quality of life based upon self-reported data. Additionally, adverse events will be assessed and recorded at all follow-up time points.

After completion of the Month 12 visit, subjects will be followed on a routine care basis at the Esophageal \& Lung Institute.

Conditions

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Barrett Esophagus Esophagus High Grade Dysplasia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TECR & ECM

Subjects undergoing TECR with ECM placement Intervention is Trans-oral Endoscopic circumferential resection (TECR) with placement of extra-cellular matrix (ECM)

Group Type EXPERIMENTAL

Subjects undergoing TECR with ECM placement (ACell MatriStem, Boston Scientific WallFlex))

Intervention Type DEVICE

TECR will be performed to resect the entire length and area of BE lesion.

ECM PLACEMENT:

Following resection, the exposed area will be covered with a 6 ply sheet of ACell MatriStem® Surgical Matrix PSMX ECM (ACell Inc., Columbia, MA). The ECM will be placed and held in position for 14 days (±4 days) using a Boston Scientific WallFlex™ Fully Covered Esophageal Stent (Boston Scientific, Boston, MA).

Interventions

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Subjects undergoing TECR with ECM placement (ACell MatriStem, Boston Scientific WallFlex))

TECR will be performed to resect the entire length and area of BE lesion.

ECM PLACEMENT:

Following resection, the exposed area will be covered with a 6 ply sheet of ACell MatriStem® Surgical Matrix PSMX ECM (ACell Inc., Columbia, MA). The ECM will be placed and held in position for 14 days (±4 days) using a Boston Scientific WallFlex™ Fully Covered Esophageal Stent (Boston Scientific, Boston, MA).

Intervention Type DEVICE

Other Intervention Names

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ACell, Inc. MatriStem® Surgical Matrix PSMX Boston Scientific, WallFlex™ Fully Covered Esophageal Stent

Eligibility Criteria

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Inclusion Criteria

1. Be at least 18 years of age and no more than 80 years of age.
2. Have an established diagnosis of HGD

a. Specific diagnosis and grading will be determined by pathology review of biopsy tissue collected during baseline EGD as part of a patient's standard of care.
3. Have no evidence of lymphovascular invasion.
4. Have no lymph node or other metastatic involvement based on EUS and FDG-PET/CT.
5. Diameter of affected tissue must warrant circumferential excision a. Subjects must have biopsy confirmed HGD in three of four esophageal quadrants at two levels spaced two centimeters apart (minimum of 6/8 biopsies indicating HGD). If two biopsies are normal (contain no HGD) they must be located on separate levels in two different quadrants.

5\. Must be an appropriate or reasonable surgical candidate. 6. Have demonstrated an understanding and signed an approved informed consent form for participation in this study.

Exclusion Criteria

1. Have lesions into or deeper than mucosal layer (superficial (T1a) Esophageal adenocarcinoma).

a. Those requiring endoscopic submucosal dissection (ESD) are not eligible for this study
2. Have presence of lymphovascular invasion.
3. Require resection length longer than 10 cm.
4. Have any lymph node or other metastatic involvement based on EUS and FDG-PET/CT.
5. Have history of any kind of previous esophageal surgery (i.e. anti-reflux surgery).
6. Are pregnant or planning to become pregnant.
7. Have coagulation disorders.
8. Have a known hypersensitivity to porcine-based materials.
9. Have an uncontrolled comorbid medical condition that would adversely affect participation in the trial.
10. Has a clinically significant psychological illness that in the physician's opinion would prohibit the subject's ability to meet the protocol requirements.
11. Are unable or unwilling to provide informed consent and/or fulfill the protocol follow-up requirements.

\-
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Integra LifeSciences Corporation

INDUSTRY

Sponsor Role collaborator

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

OTHER

Sponsor Role lead

Responsible Party

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Blair Jobe, MD

Director, Esophageal and Lung Institute

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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West Penn Allegheny Health System

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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Rice TW, Zuccaro G Jr, Adelstein DJ, Rybicki LA, Blackstone EH, Goldblum JR. Esophageal carcinoma: depth of tumor invasion is predictive of regional lymph node status. Ann Thorac Surg. 1998 Mar;65(3):787-92. doi: 10.1016/s0003-4975(97)01387-8.

Reference Type BACKGROUND
PMID: 9527214 (View on PubMed)

Witteman BP, Foxwell TJ, Monsheimer S, Gelrud A, Eid GM, Nieponice A, O'Rourke RW, Hoppo T, Bouvy ND, Badylak SF, Jobe BA. Transoral endoscopic inner layer esophagectomy: management of high-grade dysplasia and superficial cancer with organ preservation. J Gastrointest Surg. 2009 Dec;13(12):2104-12. doi: 10.1007/s11605-009-1053-x. Epub 2009 Oct 14.

Reference Type BACKGROUND
PMID: 19826883 (View on PubMed)

Badylak SF, Vorp DA, Spievack AR, Simmons-Byrd A, Hanke J, Freytes DO, Thapa A, Gilbert TW, Nieponice A. Esophageal reconstruction with ECM and muscle tissue in a dog model. J Surg Res. 2005 Sep;128(1):87-97. doi: 10.1016/j.jss.2005.03.002.

Reference Type BACKGROUND
PMID: 15922361 (View on PubMed)

Nieponice A, Gilbert TW, Badylak SF. Reinforcement of esophageal anastomoses with an extracellular matrix scaffold in a canine model. Ann Thorac Surg. 2006 Dec;82(6):2050-8. doi: 10.1016/j.athoracsur.2006.06.036.

Reference Type BACKGROUND
PMID: 17126109 (View on PubMed)

Nieponice A, McGrath K, Qureshi I, Beckman EJ, Luketich JD, Gilbert TW, Badylak SF. An extracellular matrix scaffold for esophageal stricture prevention after circumferential EMR. Gastrointest Endosc. 2009 Feb;69(2):289-96. doi: 10.1016/j.gie.2008.04.022. Epub 2008 Jul 26.

Reference Type BACKGROUND
PMID: 18657808 (View on PubMed)

Badylak SF, Hoppo T, Nieponice A, Gilbert TW, Davison JM, Jobe BA. Esophageal preservation in five male patients after endoscopic inner-layer circumferential resection in the setting of superficial cancer: a regenerative medicine approach with a biologic scaffold. Tissue Eng Part A. 2011 Jun;17(11-12):1643-50. doi: 10.1089/ten.TEA.2010.0739. Epub 2011 Mar 28.

Reference Type BACKGROUND
PMID: 21306292 (View on PubMed)

Hoppo T, Badylak SF, Jobe BA. A novel esophageal-preserving approach to treat high-grade dysplasia and superficial adenocarcinoma in the presence of chronic gastroesophageal reflux disease. World J Surg. 2012 Oct;36(10):2390-3. doi: 10.1007/s00268-012-1698-6.

Reference Type BACKGROUND
PMID: 22736346 (View on PubMed)

Buscaglia JM, Ho S, Sethi A, Dimaio CJ, Nagula S, Stavropoulos SN, Gonda TA, Poneros JM, Stevens PD. Fully covered self-expandable metal stents for benign esophageal disease: a multicenter retrospective case series of 31 patients. Gastrointest Endosc. 2011 Jul;74(1):207-11. doi: 10.1016/j.gie.2011.02.024. Epub 2011 May 6. No abstract available.

Reference Type BACKGROUND
PMID: 21549373 (View on PubMed)

Liu J, Hu Y, Cui C, Li Y, Lin X, Fu J. Removable, fully covered, self-expandable metal stents for the treatment of refractory benign esophagogastric anastomotic strictures. Dysphagia. 2012 Jun;27(2):260-4. doi: 10.1007/s00455-011-9361-1. Epub 2011 Aug 9.

Reference Type BACKGROUND
PMID: 21826422 (View on PubMed)

Bakken JC, Wong Kee Song LM, de Groen PC, Baron TH. Use of a fully covered self-expandable metal stent for the treatment of benign esophageal diseases. Gastrointest Endosc. 2010 Oct;72(4):712-20. doi: 10.1016/j.gie.2010.06.028.

Reference Type BACKGROUND
PMID: 20883848 (View on PubMed)

Eloubeidi MA, Lopes TL. Novel removable internally fully covered self-expanding metal esophageal stent: feasibility, technique of removal, and tissue response in humans. Am J Gastroenterol. 2009 Jun;104(6):1374-81. doi: 10.1038/ajg.2009.133. Epub 2009 Apr 28.

Reference Type BACKGROUND
PMID: 19491851 (View on PubMed)

Yoon CJ, Shin JH, Song HY, Lim JO, Yoon HK, Sung KB. Removal of retrievable esophageal and gastrointestinal stents: experience in 113 patients. AJR Am J Roentgenol. 2004 Nov;183(5):1437-44. doi: 10.2214/ajr.183.5.1831437.

Reference Type BACKGROUND
PMID: 15505317 (View on PubMed)

Baron TH, Burgart LJ, Pochron NL. An internally covered (lined) self-expanding metal esophageal stent: tissue response in a porcine model. Gastrointest Endosc. 2006 Aug;64(2):263-7. doi: 10.1016/j.gie.2006.03.936.

Reference Type BACKGROUND
PMID: 16860080 (View on PubMed)

Sharma P, Kozarek R; Practice Parameters Committee of American College of Gastroenterology. Role of esophageal stents in benign and malignant diseases. Am J Gastroenterol. 2010 Feb;105(2):258-73; quiz 274. doi: 10.1038/ajg.2009.684. Epub 2009 Dec 22.

Reference Type BACKGROUND
PMID: 20029413 (View on PubMed)

Hirdes MM, Siersema PD, Houben MH, Weusten BL, Vleggaar FP. Stent-in-stent technique for removal of embedded esophageal self-expanding metal stents. Am J Gastroenterol. 2011 Feb;106(2):286-93. doi: 10.1038/ajg.2010.394. Epub 2010 Oct 12.

Reference Type BACKGROUND
PMID: 20940709 (View on PubMed)

van Heijl M, Gooszen JA, Fockens P, Busch OR, van Lanschot JJ, van Berge Henegouwen MI. Risk factors for development of benign cervical strictures after esophagectomy. Ann Surg. 2010 Jun;251(6):1064-9. doi: 10.1097/SLA.0b013e3181deb4b7.

Reference Type BACKGROUND
PMID: 20485137 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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12-024

Identifier Type: -

Identifier Source: org_study_id

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