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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01393483
First received: July 11, 2011
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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 Intervention
Esophageal Cancer
Adenocarcinoma
Other: serum and tissue mesothelin

Study Type: Observational
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To evaluate prospectively what proportion of esophageal adenocarcinomas express tissue. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the correlation between serum mesothelin levels and tissue expression [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

tissue and serum


Estimated Enrollment: 300
Study Start Date: March 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Any patient seen in the gastroenterology and thoracic clinics who fits the inclusion criteria will be approached by the treating physician, the protocol investigator, or thoracic research team at Memorial Sloan-Kettering Cancer Center (MSKCC

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01393483

Contacts
Contact: Nabil Rizk, MD 212-639-8357
Contact: Prasad Adusumilli, MD 212-639-8093

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Nabil Rizk, MD    212-639-8357      
Contact: Prasad Adusumilli, MD    212-639-8093      
Principal Investigator: Nabil Rizk, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Nabil Rizk, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01393483     History of Changes
Other Study ID Numbers: 11-037
Study First Received: July 11, 2011
Last Updated: June 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
esophagectomy
endoscopy
biopsy
Tissue mesothelin
Serum mesothelin
11-037

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases

ClinicalTrials.gov processed this record on July 23, 2014