Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Participants undergo upper GI endoscopy with endoscopic mucosal resection (EMR) and/or radiofrequency ablation (RFA) of esophageal squamous dysplasia (ESD). After initial therapy participants undergo repeat endoscopy every 3 months for a year, with re-biopsy and re-treatment of residual ESD as appropriate.

Endoscopic Mucosal Resection (EMR)

Endoscopic radiofrequency ablation of regions of ESD

Radiofrequency ablation

Stephen L Burgert, MD

Esophageal cancer is common in Kenya. The precursor of esophageal cancer is esophageal squamous dysplasia (ESD). In this study, persons known to have ESD will undergo endoscopic removal or ablation of ESD in order to prevent development of esophageal cancer.

Esophageal squamous dysplasia (ESD) is the precursor lesion of esophageal squamous cell cancer. ESD causes no symptoms but can be detected by screening. ESD may harbor various grades of dysplasia. Patients with moderate grade or high grade dysplasia (MGD or HGD) have up to a 40-fold increased risk of esophageal squamous cell cancer.

In this study, persons known to have ESD with MGD or HGD on the basis of prior screening will be invited to undergo endoscopic treatment with either endoscopic mucosal resection (EMR) and/or radio frequency ablation (RFA) in order to remove or ablate regions of ESD. Participants will undergo a series of endoscopies to treat ESD and monitor success of treatment.

Endoscopic Prevention of Esophageal Cancer at Tenwek Hospital

Endoscopic Prevention of Esophageal Cancer at Tenwek Hospital (The EXPECT Trial) by Removal or Ablation of Esophageal Squamous Cell Dysplasia

The percentage of subjects demonstrating complete response defined as complete histological clearance of MGD, HGD and esophageal squamous carcinoma in the treatment areas at 12 months after the initial ablation procedure.

Percentage of participants experiencing serious adverse events following EMR or RFA treatment.

Mayo Clinic

National Cancer Institute (NCI)

Medtronic - MITG

Tenwek Hospital

Director of Endoscopy Services

Carcinoma

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Coagulants

Pharmaceutical Solutions

Iodine

Lugol's solution

Cadexomer iodine

Hemostatics

Each study participant will undergo esophageal sponge sampling using the 'EsophaCap' sponge device. Group 1 will include a safety-phase, which will consist of a lead-in cohort of 8 patients with ESCC. Subsequent recruitment of ESCC Cases (Group 1) will not commence until the Data Safety Monitoring Board (DSMB) has deemed the safety lead-in data appropriate for continuation. Following collection of esophageal cells, samples will be assessed using the EsoCAN assay. Study participant evaluations will be taken at baseline, immediately after undergoing esophageal sponge sampling, and 7 days following administration of the 'EsophaCap' device.

Each study participant will undergo (1) Esophagogastroduodenoscopy (EGD) with chromoendoscopic screening and possible biopsy, and (2) esophageal sponge sampling using the 'EsophaCap' sponge device. Pathology from chromoendoscopic screening will be used to categorize non-ESCC study participants as esophageal squamous dysplasia (ESD) cases and controls. Following collection of esophageal cells, samples will be assessed using the EsoCAN assay. Study participant evaluations will be taken at baseline, immediately after undergoing esophageal sponge sampling, and 7 days following administration of the 'EsophaCap' device.

Non-invasive strategy to sample esophageal tissue

EsophaCap Sponge

Lugol's iodine chromoendoscopy is a technique that is used to identify mucosal abnormalities of the esophagus

Chromoendoscopy

EsoCAN assay

Geoffrey Buckle, MD, MPH

Yona Ringo

Katherine Steitz, MD, MPH

In the current protocol, we propose a study to evaluate a novel, combined esophageal sponge-methylation biomarker strategy for the early detection of esophageal squamous cell carcinoma (ESCC) as well as its precursor, esophageal squamous dysplasia (ESD). This strategy leverages the 'EsophaCap', a swallowable, retrievable sponge, with subsequent evaluation of the sample using a novel molecular biomarker assay. This biomarker assay evaluates methylation levels in select genes, which have been shown to differ significantly between ESCC cases and controls in pilot studies. Detection of methylation markers highly associated with ESCC could help identify patients with concurrent ESCC or at high risk of imminently developing this condition. If successful, this strategy could result in a paradigm shift for esophageal cancer control strategies in Tanzania and other high-incidence ESCC regions.

PRIMARY OBJECTIVE:

I. To evaluate the sensitivity and specificity of a diagnostic strategy combining esophageal sponge sampling with the 'EsophaCap' sponge device with use of the EsoCAN assay, a novel molecular biomarker assay, among patients with histologically-confirmed ESCC cases and controls.

SECONDARY OBJECTIVES:

I. To evaluate the sensitivity and specificity of a diagnostic strategy combining esophageal sponge sampling with the 'EsophaCap' sponge device with use of the the EsoCAN assay, among patients with histologically-confirmed ESD and controls.

II. To evaluate the safety and feasibility of 'EsophaCap' a swallowable and retrievable sponge, as a non-invasive strategy for screening and early detection of ESCC and its precursor, ESD, in Tanzania.

EXPLORATORY OBJECTIVES:

I. Sensitivity and specificity of esophageal sponge sampling with standard cytological examination among histologically-confirmed ESCC cases and controls.

II. Sensitivity and specificity of esophageal sponge sampling with standard cytological examination among histologically-confirmed ESD cases and controls.

III. To examine methylation levels in new and previously identified genes among patients recruited as suspected ESCC cases who are found to have an alternative diagnosis, with the goal of optimizing the EsoCAN Assay.

OUTLINE:

Each participant will undergo esophageal sponge sampling suing the 'EsophaCap' sponge device. Participants will be on study for up to 38 days.

Novel Strategy for Early Detection of Esophageal Squamous Cell Carcinoma

Investigation of a Novel Strategy for Early Detection of Esophageal Squamous Cell Carcinoma

The proportion of participants with a positive EsoCAN assay result, among patients with histologically-confirmed Esophageal Squamous Cell Carcinoma (ESCC). The following equation will be used as a cut point for ESCC using the EsoCAN assay \[0.139\*log2(gene A)\] + \[0.176\* log2(gene B)\] + \[0.185\* log2(gene C)\], whereas a cutoff value (for the numerical index produced by this formula) of greater than -2.327 is classified as positive.

The proportion of participants with a negative EsoCAN assay result for will be reported, among study participants who are classified as controls. The following equation will be used as a cut point for ESCC using the EsoCAN assay \[0.139\*log2(gene A)\] + \[0.176\* log2(gene B)\] + \[0.185\* log2(gene C)\], whereas a cutoff value (for the numerical index produced by this formula) of less than -2.327 is classified as negative.

The proportion of participants with both a positive EsoCAN assay result, among patients with histologically-confirmed Esophageal Squamous Dysplasia (ESD). The following equation will be used as a cut point for ESD: \[0.139\*log2(gene A)\] + \[0.176\* log2(gene B)\] + \[0.185\* log2(gene C)\], whereas a cutoff value (for the numerical index produced by this formula) of greater than -2.327 is classified as positive.

The proportion of participants with a negative EsoCAN assay result will be reported. The following equation will be used as a cut point for ESD: \[0.139\*log2(gene A)\] + \[0.176\* log2(gene B)\] + \[0.185\* log2(gene C)\], whereas a cutoff value (for the numerical index produced by this formula) of less than -2.327 is classified as negative.

The success of swallowing the esophageal sponge device will be determined by the clinical team overseeing the EsophaCap' administration and categorized as a dichotomous response of Yes (successful) or No (not successful).

Adverse events for the lead in cohort with histologically confirmed or suspected ESCC based upon pre-specified clinical criteria will be reported and graded and classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Participants will be asked to rate their satisfaction with their experience with the EsophaCap sponge procedure after the procedure is complete by selecting a score on a scale with corresponding facial images with scores ranging between 0='Best Experience' (large smile on facial expression) to 10='Worst experience' (crying and frowning facial expression).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Endoscopic Prevention of Esophageal Cancer at Tenwek Hospital	NCT02146508	Esophageal Canc... Esophageal Squa...	Endoscopic Muco... Radiofrequency ...	18 Years - 85 Years	Tenwek Hospital
Novel Strategy for Early Detection of Esophageal Squamous Cell Carcinoma	NCT05028725	Esophageal Squa... Esophageal Squa...	EsophaCap Spong... Chromoendoscopy EsoCAN assay	18 Years -	University of California, San Francisco
Endoscopic Prevention of Esophageal Cancer at Tenwek Hospital	NCT02146508	Esophageal Canc... Esophageal Squa...	Endoscopic Muco... Radiofrequency ...	18 Years - 85 Years	Tenwek Hospital
Novel Strategy for Early Detection of Esophageal Squamous Cell Carcinoma	NCT05028725	Esophageal Squa... Esophageal Squa...	EsophaCap Spong... Chromoendoscopy EsoCAN assay	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for esophageal squamous dysplasia