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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01393483

Collaborator

(none)

371

Enrollment

Location

138.1

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer Adenocarcinoma	Other: serum and tissue mesothelin Other: serum and tissue mesothelin Other: serum and tissue mesothelin

Study Design

Study Type:

Observational

Actual Enrollment :

371 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Esophageal Adenocarcinoma (EAC)

Actual Study Start Date :

Mar 1, 2011

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
patients endoscopically resected 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.	Other: serum and tissue mesothelin Tissue mesothelin staining at the time of the initial endoscopy, and of any subsequent biopsy specimen during the endoscopic screening period. Serum mesothelin level at the time of initial endoscopy, and at each subsequent endoscopy for two years or until disease recurs.
patients treated primarily with surgery 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.	Other: serum and tissue mesothelin Tissue mesothelin staining on the surgically resected esophageal specimen. Serum mesothelin level at the time of surgical resection, and at each follow-up clinic visit for two years or until disease recurs.
patients who undergo chemo-radiation prior to surgery 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.	Other: serum and tissue mesothelin Tissue mesothelin staining on the initial endoscopic specimen (typically obtained when an EUS is done) and on the surgically resected esophageal specimen Serum mesothelin level prior to initiation of induction chemotherapy, at the time of the post-induction PET, at the time of surgical resection, and at each follow-up clinic visit for two years or until disease recurs.

Arm

Intervention/Treatment

patients endoscopically resected

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.

Other: serum and tissue mesothelin

Tissue mesothelin staining at the time of the initial endoscopy, and of any subsequent biopsy specimen during the endoscopic screening period. Serum mesothelin level at the time of initial endoscopy, and at each subsequent endoscopy for two years or until disease recurs.

patients treated primarily with surgery

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.

Other: serum and tissue mesothelin

Tissue mesothelin staining on the surgically resected esophageal specimen. Serum mesothelin level at the time of surgical resection, and at each follow-up clinic visit for two years or until disease recurs.

patients who undergo chemo-radiation prior to surgery

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.

Other: serum and tissue mesothelin

Tissue mesothelin staining on the initial endoscopic specimen (typically obtained when an EUS is done) and on the surgically resected esophageal specimen Serum mesothelin level prior to initiation of induction chemotherapy, at the time of the post-induction PET, at the time of surgical resection, and at each follow-up clinic visit for two years or until disease recurs.

Outcome Measures

Primary Outcome Measures

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 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.
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

Secondary Outcome Measures

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).
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 for the presence of any confounders in the putative association between serum mesothelin expression and the risk of recurrence [2 years]
To evaluate the correlation between serum mesothelin levels and tissue expression [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

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.