Evaluate Mesothelin as a Biomarker for the Clinical Management of Esophageal Adenocarcinoma (EAC)

Completed

• Conditions: Esophageal Cancer; Adenocarcinoma
• Interventions: Other: serum and tissue mesothelin

• Registration Number: NCT01393483
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary

The purpose of this study is to find out whether a protein, called mesothelin, found in the blood and tissue can be used as "marker" for esophageal cancer. Doctors at Memorial Sloan-Kettering Cancer Center would like to compare levels of this protein in patients with abnormal cells or tissue of the esophageal to the levels of this protein in patients being treated for cancer for the esophagus.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-07-11
• Study First Submitted QC: 2011-07-12
• Study First Posted: 2011-07-13
• Status Verified: 2024-10
• Primary Completion: 2024-10-22
• Study Completion: 2024-10-22
• Last Update Submitted: 2024-10-24
• Last Update Posted: 2024-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 371

Inclusion Criteria

• Patients with T1 adenocarcinoma or suspected adenocarcinoma who are scheduled for a biopsy and mucosal resection (Group 1)
• Patients with a T1-2N0 adenocarcinoma or suspected adenocarcinoma who are scheduled to undergo and esophagectomy (Group 2)
• Patients with T2N1 and T3N0-1 adenocarcinoma or suspected adenocarcinoma who are scheduled to undergo endoscopy and biopsy and/or endoscopic ultrasound and biopsy prior to pre-operative chemo-radiotherapy and have baseline and surgical tissue available for staining (Group 3)

Read More

Exclusion Criteria

• Patients <18 years of age
• Patients unfit medically for endoscopy surveillance and therapy
• Patients unfit medically for esophagectomy
• Patients with stage IV esophageal adenocarcinoma
• Patients previously treated with chemo-radiotherapy for their esophageal cancer
• Patients with squamous cell carcinoma of the esophagus
• Patients who have a history of cancer within 3 years or have a concurrent cancer.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
patients treated primarily with surgery	serum and tissue mesothelin	In patients who undergo surgery as their primary therapy, serum will be obtained at the time of surgical resection, and at each subsequent long-term disease status follow-up visit every 4 (+/- 2) months.
patients who undergo chemo-radiation prior to surgery	serum and tissue mesothelin	a serum sample will be obtained : 1) prior to initiation of therapy, 2) following the completion of induction chemotherapy, 3) at the time of surgical resection, and 4) at each subsequent long-term disease status follow-up visit every 4 (+/- 2) months. The availability of tissue for staining will determine whether or not patients are evaluable for Group 3.
patients endoscopically resected	serum and tissue mesothelin	In patients with endoscopically resected T1 disease (40 patients in 2 years) if available, we will stain the initial endoscopic tumor specimen, as well as any subsequent specimen obtained at each routine 3(+/- 2) month interval endoscopy.

Primary Outcome Measures

Name	Time	Method
To evaluate prospectively what proportion of esophageal adenocarcinomas express tissue.	2 years	The investigators will examine the range and variability in the percentage on cells stained (for TM) and in the absolute value (for SM). TM expression is commonly analyzed in a binary fashion, with 25% of cells stained indicating positive expression (per standard pathological guidelines for tissue staining)
To evaluate prospectively if clinical response to induction chemotherapy	2 years	First, the investigators will use two-sample t-tests to determine whether the initial responders to induction chemotherapy (defined as \>30% decrease in SUV at the repeat PET) differ from non-responders in their 1) baseline (pre-induction) SM value, and 2) percent change in SM value between pre-induction and mid-induction (after 2 cycles) evaluations.
To evaluate prospectively if clinical response to concurrent chemo-radiation correlates to serum mesothelin levels	2 years	The investigators will take the following steps in order to assess the ability of SM at the time of resection with curative intent to predict disease recurrence: 1) we will examine the association between SM and the risk of recurrence by fitting a Cox proportional hazards model (after appropriate transformation of the SM value and checking of the PH assumption
To evaluate prospectively if serum mesothelin levels correlate to clinical stage in esophageal adenocarcinomas	2 years	The investigators will explore the optimal cut point that defines positive expression. Serum mesothelin (SM) will be measured and analyzed whenever possible on a continuous scale.

Secondary Outcome Measures

Name	Time	Method
To evaluate for the presence of any confounders in the putative association between serum mesothelin expression and the risk of recurrence	2 years
To evaluate whether expression of tissue mesothelin is a predictor of poor response to chemotherapy	2 years	Mesothelin positive tumors (MES+) will be defined as strong staining in \> 25% of the tumor cells and mesothelin negative tumors (MES-) are defined as \<= 25% cytoplasmic staining. Serum mesothelin will be collected and analyzed, whenever possible, on a continuous scale.
To evaluate the correlation between serum mesothelin levels and tissue expression	2 years
To evaluate whether expression of tissue mesothelin is a predictor of recurrence	2 years	The investigators will Wilcoxon test to investigate the association between serum mesothelin and tissue mesothelin at each time point where both markers are evaluated, and will further attempt to obtain an aggregate measure of this correlation using clustered Wilcoxon test, which accounts for multiple measurements per patient (14).

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States