Investigation of a Novel Strategy for Early Detection of Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Esophageal Squamous Cell Carcinoma
- Sponsor
- University of California, San Francisco
- Enrollment
- 289
- Locations
- 1
- Primary Endpoint
- Proportion of True-Positives (sensitivity) detected with the EsoCAN assay after specimen collection using 'EsophaCap' sponge sampling (ESCC cases & controls only)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •ESCC Cases (Group 1):
- •Male or female \>= 18 years of age at screening visit.
- •Patients are currently seen for clinical care at Muhimbili National Hospital (MNH)-Upanga or at MNH-Mloganzila.
- •Patient meets one of the following two criteria-
- •Patients with a confirmed diagnosis of ESCC as evidenced by histological confirmation OR
- •Patient planned to undergo EGD with biopsy for suspected ESCC based upon any one of the following clinical criteria: (1) findings on computed tomography (CT) scan; (2) findings on barium swallow; (3) findings on endoscopy without biopsy confirmation, (4) symptoms of dysphagia and/or odynophagia without an alternative explanation for these symptoms.
- •Patient must be able to swallow liquid (Ogilvie's score \< 3).
- •Patients must be well enough to participate in a 20-minute interview or have a close relative who is able to do so on their behalf.
- •Patients must be willing to be contacted either in person or via phone 7-10 days following administration of the 'EsophaCap' sponge device.
- •Native of Tanzania.
Exclusion Criteria
- •ESCC Cases (Group 1):
- •Known pregnancy during participation in the study.
- •Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- •Clinical instability (i.e. hypotension or a recent cardiovascular event).
- •Any history of upper gastrointestinal bleeding within the past 3 months (including reported history of hematemesis and/or melena).
- •Diagnosis of peptic ulcer disease within the last 3 months.
- •Known history of esophageal varices.
- •Patients taking anticoagulation or antiplatelet therapy/medication (warfarin, clopidogrel, aspirin, heparin or enoxaparin) for high-risk conditions.
- •Patients with an active extra-esophageal malignancy (not currently in remission).
- •Patient with a known history of a non-malignant esophageal stricture.
Outcomes
Primary Outcomes
Proportion of True-Positives (sensitivity) detected with the EsoCAN assay after specimen collection using 'EsophaCap' sponge sampling (ESCC cases & controls only)
Time Frame: Up to 38 days
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.
Proportion of True-Negatives (specificity) detected with the EsoCAN assay after specimen collection using 'EsophaCap' sponge sampling (ESCC cases & controls only)
Time Frame: Up to 38 days
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.
Secondary Outcomes
- Proportion of True-Positives (sensitivity) detected with the EsoCAN assay after specimen collection using 'EsophaCap' sponge sampling (ESD cases & controls only)(Up to 38 days)
- Median Acceptability Scores(Up to 38 days)
- Proportion of True-Negatives (specificity) detected with the EsoCAN assay after specimen collection using 'EsophaCap' sponge sampling (ESD cases & controls only)(Up to 38 days)
- Proportion of study participants who successfully swallow the esophageal sponge device(Up to 38 days)
- Proportion of study participants who experienced an esophageal sponge device-related adverse event in the lead in cohort of ESCC Cases(Up to 38 days)