Early Detection of Esophageal Squamous Cancer With the Capsule Sponge Device

NCT ID: NCT06418516

Last Updated: 2024-05-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2027-06-01

Brief Summary

Esophageal squamous cell carcinoma accounts for ~90% of the nearly half-million annual incident cases of esophageal cancer worldwide. The high costs and invasiveness of upper endoscopy constitute a limitation in providing adequate surveillance for at-risk individuals, including those with previous head and neck cancer. The ANGELA study is a prospective evaluation of the minimally-invasive capsule-sponge device, coupled with tissue biomarkers (p53-immunohistochemistry), to detect squamous neoplasia in high-risk individuals.

Detailed Description

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer worldwide, accounting for nearly 90% of the 456,000 incident cases of esophageal cancer each year. Overall, it is the seventh most common malignancy and the sixth most common cause of cancer-related mortality, with a high incidence rate in eastern to central Asia and eastern and southern Africa. This cancer is more common in men (~70%), and the main risk factors include cigarette smoking, alcohol consumption, poor oral hygiene, the ingestion of caustic agents, and nutritional deficiencies. Additionally, an increased risk of ESCC following curative treatment of head and neck cancer (HNC) has been well-documented in the literature, with a lifetime incidence ranging between 3.8% and 14.9% in prospective observational studies. The carcinogenesis of ESCC is sequential and preceded by several precancerous stages, including low-grade intraepithelial neoplasia (LG-IEN) and, subsequently, high-grade intraepithelial neoplasia (HG-IEN).

Although the prognosis of ESCC is extremely poor, with 5-year survival below 20%, it dramatically improves if the disease is detected at an early stage. Consequently, mass screening in high-incidence regions is being widely debated. However, population-wide screening presents a large challenge in terms of cost-effectiveness and manpower, as currently, a potential screening regime for ESCC would rely on endoscopic examination with biopsies, which remains the gold standard for ESCC diagnosis. Furthermore, since around 80% of all ESCCs occur in economically less-developed regions, newer, cheaper, and less invasive diagnostic tools are highly warranted.

The capsule-sponge is a novel, minimally-invasive device that collects cells from the esophagus to produce a pseudo-biopsy suitable for routine laboratory analysis. In addition, tissue biomarkers such as p53 immunohistochemistry (p53-IHC) and molecular testing, including copy number assays to detect aneuploidy, can be applied. There is extensive data on the use of this technology for early diagnosis of Barrett's esophagus (precursor to adenocarcinoma), which has now reached wide clinical implementation in the UK National Health Service. Building on the promising pilot data, the current study aims to expand further our previously developed clinical assay for early detection of esophageal squamous neoplasia using the capsule-sponge device coupled with biomarkers and machine learning technologies.

In this prospective trial, we plan to recruit patients within three risk groups for ESCC: 1. healthy controls; 2. high-risk individuals (previous head-and-neck cancer/ESCC); and 3. patients with known early ESCC. Each patient will undergo a high-definition endoscopy and a capsule-sponge examination. The biomarker assay, including p53-IHC and shallow whole genome sequencing, will be tested within the capsule-sponge samples and compared with the final endoscopic diagnosis. Machine learning algorithms will be applied to digitalized cytology to detect atypical cells and regions of p53-IHC overexpression. Lastly, we will extract microbial DNA from capsule-sponge samples to assess any taxonomic diversity within the three risk groups for ESCC.

We hope to develop a novel, effective, and affordable diagnostic assay that, coupled with a minimally-invasive capsule-sponge device, could be implemented in a clinical setting, improving the early detection of ESCC and, eventually, patient outcomes.

Conditions

Esophageal Cancer; Head and Neck Cancer; Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Capsule-sponge

This part of the study will have an active prospective recruitment of patients. Recruitment will involve three patient populations:

1. Patients with ESCC

2. Patients at high risk for ESCC

3. Healthy controls

Following inclusion in the study, subjects will be asked to complete a behavior questionnaire, have blood collected, and undergo a capsule-sponge procedure followed by diagnostic gastroscopy using advanced imaging with biopsies. During gastroscopy, additional tissue samples will be collected for research purposes. These samples, along with cytological specimens from the capsule-sponge, will be analyzed to assess the diagnostic accuracy of biomarkers in the diagnosis of esophageal squamous neoplasia.

Group Type: EXPERIMENTAL

Capsule-sponge

Intervention Type: DEVICE

The capsule-sponge is a minimally-invasive sampling device consisting of a polyurethane sponge compressed in a cellophane capsule attached to a string. When swallowed, the capsule dissolves in the stomach, releasing the cell collection sponge that expands to 3 cm in diameter. Next, a nurse or qualified medical technician retrieves the sponge by pulling back on the string and retracting it through the mouth. During extraction, the rough texture on the surface of the sponge collects epithelial cells in the cardia and along the entire length of the esophagus.

Interventions

Capsule-sponge

The capsule-sponge is a minimally-invasive sampling device consisting of a polyurethane sponge compressed in a cellophane capsule attached to a string. When swallowed, the capsule dissolves in the stomach, releasing the cell collection sponge that expands to 3 cm in diameter. Next, a nurse or qualified medical technician retrieves the sponge by pulling back on the string and retracting it through the mouth. During extraction, the rough texture on the surface of the sponge collects epithelial cells in the cardia and along the entire length of the esophagus.

Intervention Type: DEVICE

Other Intervention Names

Upper endoscopy with biopsies; Blood collection; throat swab

Eligibility Criteria

Inclusion Criteria

1. Patients with esophageal squamous cell cancer (ESCC):

• Patients ≥18 years of with adequate performance status for endoscopy
• Newly diagnosed ESCC suitable for endoscopic or oncological treatment (Rth/Chth)
• Patients currently undergoing oncological treatment (Rth/Chth)
• Consent to provide tissue samples for the study
• Dysphagia grade ≤2 (able to swallow mixed foods and tablets)

2. Patients at high risk for ESCC:

• Patients ≥18 years of age with adequate performance status for endoscopy
• Prior definitive treatment for head and neck cancer (cancer of the oral cavity, hypopharyngeal cancer, laryngeal carcinoma) and at least 12 months post-therapy (both Rth, Chth, and combination treatment)
• Prior definitive endoscopic treatment for early ESCC in the past (at least 6 months since completion)
• Consent to provide tissue samples for the study
• Dysphagia grade ≤2

3. Healthy controls - Patients ≥18 years old undergoing endoscopic evaluation for typical GI symptoms other than dysphagia (e.g., GERD, dyspepsia, etc.) without significant risk factors for ESCC

Exclusion Criteria

• Patients currently on anticoagulant treatment (warfarin, acenocoumarol) with no possibility of stopping / modification
• Dysphagia grade ≥3 (able to swallow only liquid foods)
• History of myocardial infarction or other cardiovascular event within 6 months of enrolment
• Neurological diseases associated with impaired swallowing
• Patients in long-term care or institutional care (physical, psycho-social disorders, intellectual disability).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maria Sklodowska-Curie National Research Institute of Oncology

OTHER

Sponsor Role: collaborator

Centre of Postgraduate Medical Education

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wladyslaw Januszewicz, M.D., PhD

Role: PRINCIPAL_INVESTIGATOR

Centre of Postgraduate Medical Education, Warsaw, Poland

Central Contacts

Wladyslaw Januszewicz, M.D., PhD

Role: CONTACT

wjanuszewicz@cmkp.edu.pl

+48225462328 ext. +48

Jaroslaw Regula, M.D., PhD

Role: CONTACT

jaroslaw.regula@coi.pl

+48225462328 ext. +48

Other Identifiers

439/2023

Identifier Type: -

Identifier Source: org_study_id