Esophageal Cytology With FISH in Detecting Esophageal Cancer

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02100189
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 50
• Location: 1
• Arm: 1
• Duration (Months): 21.9
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This clinical trial studies whether esophageal cytology plus fluorescence in situ hybridization (FISH) is equal to or better than esophago-gastro-duodenoscopy (EGD) or upper endoscopy for the early detection of esophageal cancer. Genes are the units of deoxyribonucleic acid (DNA) the chemical structure carrying genetic information that determine many human characteristics. Certain genes in cancer cells may determine how the tumor grows or spreads and how it may respond to different drugs. Part of this study is to test those genes in esophageal cells using FISH.

Condition or Disease	Intervention/Treatment	Phase
Dysphagia; Dysplasia; Esophageal Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Esophagitis; Gastroesophageal Reflux Disease; High Grade Dysplasia in Barrett Esophagus; Weight Loss	Other: Cytology Specimen Collection Procedure; Procedure: Esophagogastroduodenoscopy; Other: Laboratory Biomarker Analysis	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. Determine if sponge cytology with FISH is a reliable screening tool for esophageal dysplasia/cancer, and determine its sensitivity and specificity, compared to the gold standard procedure (upper endoscopy).

SECONDARY OBJECTIVES:

1. Determine if the cytology screening with FISH biomarkers is more cost effective than upper endoscopy for the screening of esophageal cancer and the surveillance of esophageal metaplasia and dysplasia.

2. Determine the limitations and future needs to improve this technique.

OUTLINE:

Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Esophageal Cancer (10030139, 10066354) Screening With FISH in Esophageal Cytology
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Screening (esophageal cytology, FISH) Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.	Other: Cytology Specimen Collection Procedure; Undergo esophageal cytology collection; Other Names: Cytologic Sampling ; Procedure: Esophagogastroduodenoscopy; Undergo standard EGD or endoscopy; Other Names: EGD ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Sensitivity of Sponge Cytology Using FISH [At the time of sponge cytology and EGD]

   All processed (FISH) esophageal cells will be compared to the final pathologic esophageal diagnoses determined by EGD or surgical resection to assess the test's sensitivity and specificity for the diagnosis of esophageal cancer. Using EGD diagnostic outcomes as the gold standard, the sensitivity and specificity will be computed with corresponding 95% confidence interval of the FISH sponge cytology test in the study population.

2. Specificity of Sponge Cytology Using FISH [At the time of sponge cytology and EGD]

   All processed (FISH) esophageal cells will be compared to the final pathologic esophageal diagnoses determined by EGD or surgical resection to assess the test's sensitivity and specificity for the diagnosis of esophageal cancer. Using EGD diagnostic outcomes as the gold standard, the sensitivity and specificity will be computed with corresponding 95% confidence interval of the FISH sponge cytology test in the study population.

Secondary Outcome Measures

1. Adverse Events Associated With FISH Sponge Cytology Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [At the time of sponge cytology procedure]

   Descriptive statistics will be used to summarize all adverse events associated with FISH sponge cytology test.

2. Tolerability of FISH Spongy Cytology [After completion of FISH and EGD]

   Tolerability is defined as the patient's willingness to repeat procedure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects with known esophageal cancer diagnosed by previous endoscopy

• Adenocarcinoma

• Squamous cell carcinoma

• Patients determined to be at risk for esophageal cancer:

• Subjects with a history of Barrett's esophagus

• Subjects with a history of low or high grade dysplasia

• Subjects with a history of gastroesophageal reflux disease (GERD)

• Subjects with a history of esophagitis

• Subjects with symptoms of esophageal cancer (EC) referred for endoscopy (new onset dysphagia, weight loss, etc)

• Patients must be scheduled for a procedure capable of providing a definitive pathological diagnosis and evaluating for complications of the esophageal sponge on the same day as the study procedure, either:

• Upper endoscopy

• Surgical esophagectomy

• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (Karnofsky >= 30%) will be included

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Subjects with severe, symptomatic dysphagia (unable to pass solids)

• Subjects that are unable to swallow a tablet/pill for any reason

• Subjects with a previous esophagectomy

• Subjects with esophageal varices

• Subjects unable to provide consent

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Hunter, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Hunter, Interim Dean, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT02100189
• Other Study ID Numbers: IRB00009213; NCI-2014-00384; IRB00009213; P30CA069533
• First Posted: Mar 31, 2014
• Last Update Posted: May 11, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Barrett Esophagus; Gastroesophageal Reflux; Esophagitis; Weight Loss

Study Results

Participant Flow

Arm/Group Title	Esophageal Cell Harvesting Procedure
Arm/Group Description	Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.
Period Title: Overall Study
STARTED	50
COMPLETED	50
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Esophageal Cell Harvesting Procedure
Arm/Group Description	Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (13.4)
Sex: Female, Male (Count of Participants)
Female	18 36%
Male	32 64%
Region of Enrollment (participants) [Number]
United States	50 100%
Body Mass Index, average (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.5 (7.66)
Number of participants with history of GERD (Count of Participants)
Count of Participants [Participants]	38 76%
Number of participants with history of Barrett's Esophagus (Count of Participants)
Count of Participants [Participants]	28 56%
Number of participants with a history of PPI use (Count of Participants)
Count of Participants [Participants]	39 78%

Outcome Measures

1. Primary Outcome

Title	Sensitivity of Sponge Cytology Using FISH
Description	All processed (FISH) esophageal cells will be compared to the final pathologic esophageal diagnoses determined by EGD or surgical resection to assess the test's sensitivity and specificity for the diagnosis of esophageal cancer. Using EGD diagnostic outcomes as the gold standard, the sensitivity and specificity will be computed with corresponding 95% confidence interval of the FISH sponge cytology test in the study population.
Time Frame	At the time of sponge cytology and EGD

Outcome Measure Data

Analysis Population Description

Analysis was per protocol

Arm/Group Title	Esophageal Cell Harvesting Procedure
Arm/Group Description	Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.
Measure Participants	50
Number (95% Confidence Interval) [percentage of cases among positive tests]	13.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Esophageal Cell Harvesting Procedure
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	13.30
	Confidence Interval	(2-Sided) 95%; 3.76 to 30.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.062
	Estimation Comments	Exact Binomial confidence interval.

2. Primary Outcome

Title	Specificity of Sponge Cytology Using FISH
Description	All processed (FISH) esophageal cells will be compared to the final pathologic esophageal diagnoses determined by EGD or surgical resection to assess the test's sensitivity and specificity for the diagnosis of esophageal cancer. Using EGD diagnostic outcomes as the gold standard, the sensitivity and specificity will be computed with corresponding 95% confidence interval of the FISH sponge cytology test in the study population.
Time Frame	At the time of sponge cytology and EGD

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Esophageal Cell Harvesting Procedure
Arm/Group Description	Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.
Measure Participants	50
Number (95% Confidence Interval) [Percentage of non-cases among neg tests]	94.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Esophageal Cell Harvesting Procedure
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	94.7
	Confidence Interval	(2-Sided) 95%; 73.97 to 99.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.051
	Estimation Comments	Exact binomial confidence interval

3. Secondary Outcome

Title	Adverse Events Associated With FISH Sponge Cytology Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description	Descriptive statistics will be used to summarize all adverse events associated with FISH sponge cytology test.
Time Frame	At the time of sponge cytology procedure

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT)

Arm/Group Title	Esophageal Cell Harvesting Procedure
Arm/Group Description	Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.
Measure Participants	50
Number [adverse events]	16

4. Secondary Outcome

Title	Tolerability of FISH Spongy Cytology
Description	Tolerability is defined as the patient's willingness to repeat procedure.
Time Frame	After completion of FISH and EGD

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT)

Arm/Group Title	Esophageal Cell Harvesting Procedure
Arm/Group Description	Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.
Measure Participants	50
Number [percentage of subjects tolerating test]	100

Adverse Events

Time Frame	Adverse Events were collected on patients from time of consent to completion of cell harvesting procedure, up to 24 hours.
Arm/Group Title	Esophageal Cell Harvesting Procedure
Arm/Group Description	Participants swallow the capsule (Oesotest from Actimed) and then wait 10 minutes before the sponge is pulled out through the esophagus by gentle traction on the string. Cytology samples from the sponge are harvested and analyzed by FISH. Participants then undergo standard EGD or upper endoscopy.
All Cause Mortality
	Esophageal Cell Harvesting Procedure
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Esophageal Cell Harvesting Procedure
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Other (Not Including Serious) Adverse Events
	Esophageal Cell Harvesting Procedure
	Affected / at Risk (%)	# Events
Total	16/50 (32%)
Gastrointestinal disorders
Gagging / Discomfort	14/50 (28%)	14
Emesis	2/50 (4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.