Pancreatic Intraepithelial Neoplasia (PanIN) and the Association With Recurrence of Pancreatic Adenocarcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cold Spring Harbor Laboratory
Information provided by (Responsible Party):
Wendy K. Chung, Columbia University
ClinicalTrials.gov Identifier:
NCT01219829
First received: October 11, 2010
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

Pre-invasive intraepithelial neoplasms (PanIN) have been identified as precursor lesions to pancreatic cancer. While there is growing evidence supporting PanIN's genetic links to pancreatic adenocarcinoma, the natural history of these lesions has not been well-established. Thus, through this study, the investigators are interested in examining the microscopic and genetic characteristics of PanIN lesions in two "high-risk" patient groups: 1)patients who underwent surgery for pancreatic cancer and developed tumor recurrence after surgery and 2) patients with a strong family history of pancreatic cancer or with a genetic syndrome that puts them at risk for pancreas cancer.

The investigators hypothesize that field carcinogenesis, neoplasia in surrounding tissue around the primary tumor site, is an important mechanism of local recurrence in sporadic pancreatic adenocarcinoma and of primary tumorigenesis in familial pancreatic cancer.


Condition
Pancreatic Cancer

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Refining the Molecular Progression From Intraductal to Invasive Pancreatic Cancer: Correlating Genetic Profiles and Clinicopathological Phenotypes in Sporadic and Familial Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Primary Outcome: Distinct histological features of PanIN lesions [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Our first aim is to assess for distinctive histological features of PanIN within surgical specimens of our two study groups.


Secondary Outcome Measures:
  • Secondary Outcome: Clonality of Multifocal PanIN Lesions [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Our secondary aim is to evaluate clonality of multifocal PanIN lesions by utilizing microarray-based comparative genomic hybridization (aCGH).

  • Secondary Outcome: Evaluation of Recurrence Mechanism in PC [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    aCGH will also be utilized to evaluate recurrence mechanism in a set of cases in which both original tumor and recurrence tumor was resected, allowing for clonal origins to be evaluated.


Biospecimen Retention:   Samples With DNA
  • Tissue: Pancreatic resection specimens will be obtained from our Pancreatic Cancer Tissue Bank and evaluated by a single pathologist, blinded to patients' clinical information. Specimens will be examined for PanIN lesions, specifically number and grade of lesions, the presence of multifocality and lesion location in relation to tumor.
  • Molecular Analysis: In patients with multifocal PanIN disease outside tumor location, molecular analysis will be conducted to determine clonality of these PanIN lesions. In any patient who underwent a second resection for recurrent Pancreatic ductal adenocarcinoma , the recurrent tumor will also be studied. All neoplastic lesions of interest will be laser-microdissected from paraffin-embedded slides.
  • ROMA analysis: Genomic DNA from PanIN lesions and tumor will be isolated, using representational oligonucleotide microarray analysis (ROMA) or somatic mutation analysis. ROMA analysis will be performed by Cold Spring Harbor Laboratory.

Estimated Enrollment: 20
Study Start Date: August 2008
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Family History patients
Patients with a strong family history of pancreatic cancer or with a genetic syndrome that puts them at risk for pancreas cancer.
Recurrence patients
Patients who underwent surgery for pancreatic cancer and developed tumor recurrence after surgery
Control Group
A control Pancreatic ductal adenocarcinoma (PDC) patient from the Registry will also be identified for each study patient, matched by age, stage, history of neoadjuvant chemotherapy/radiation and smoking status.

Detailed Description:

Pancreatic adenocarcinoma (PC) is the fourth leading cause of cancer-related death in the United States.Despite advances in chemotherapeutics and surgical care, the prognosis for PC patients remains dismal, even following surgery with curative intent. In order to improve outcomes, the best hope will be to target preinvasive PanIN lesions for screening and therapy. Prior to this, however, the natural history of PanIN lesions needs to be better elucidated. A novel model to study PanIN progression is by examination of cases of local recurrence following surgical resection. We have previously reported our findings from histopathological review of such cases. Compared to matched controls, locally-recurrent PC patients were significantly more likely to exhibit a pattern of multifocal, diffuse PanIN in their original resection tissue. This is similar to the pattern of multifocal PanIN that has been demonstrated from small prospective screening studies of familial PC kindreds

These analyses support our hypothesis that field carcinogenesis may be an important mechanism in PC. The objective of our study is to evaluate for pathological and molecular evidence of a field effect in locallyrecurrent and familial PC. Our first aim is to assess for distinctive histological features of PanIN within surgical specimens of our two study groups. Secondly, clonality of multifocal PanIN will be assessed utilizing microarraybased comparative genomic hybridization (aCGH). Finally, aCGH will also be utilized to evaluate recurrence mechanism in a set of cases in which both original tumor and recurrence tumor was resected, allowing for clonal origins to be evaluated.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

We are interested in studying two "high-risk" patient groups:

  1. patients who underwent surgery for pancreatic cancer and developed tumor recurrence after surgery and
  2. patients with a strong family history of pancreatic cancer or with a genetic syndrome that puts them at risk for pancreas cancer.
Criteria

Inclusion Criteria:

  • Tissue-confirmed diagnosis of pancreatic adenocarcinoma.
  • Underwent surgical resection for adenocarcinoma at Columbia-Presbyterian Medical Center with pathologically negative surgical margins.
  • Enrolled in our Pancreatic Cancer Registry and Tissue Bank protocol (AAAA-6154).
  • Have at least 2 relatives (of whom one must be first-degree relative) with pancreatic cancer, or have been diagnosed with a a genetic syndrome which is associated with pancreatic cancer (among the included syndromes include BRCA1/2, FAMMM, Peutz-Jeghers, HNPCC, Hereditary Pancreatitis) —OR—
  • Have radiological or pathological (fine needle aspirate or surgical biopsy) evidence of local tumor recurrence following surgery.

Exclusion Criteria:

  • Metastatic disease discovered at presentation or on recurrence (exception is the familial PDC patients)
  • Positive surgical margins.
  • Lack of clinical followup at one year following surgery
  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: NCT01219829

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Cold Spring Harbor Laboratory
Investigators
Principal Investigator: Wendy K Chung, MD Columbia University
  More Information

No publications provided

Responsible Party: Wendy K. Chung, Assistant Professor of Pediatrics, Molecular Genetics, Columbia University
ClinicalTrials.gov Identifier: NCT01219829     History of Changes
Other Study ID Numbers: AAAD5381, AAAD-5381
Study First Received: October 11, 2010
Last Updated: February 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Pancreatic intraepithelial neoplasia (PanIN)
Pancreatic Cancer
Recurrence of pancreatic cancer
Field Effect
Genetic mutations in pancreatic cancer

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases

ClinicalTrials.gov processed this record on October 23, 2014