Pancreatico-biliary Tumor Mutation Profiling in Bile Samples (ONCOBIL)

Tumor Mutation Profiling in Bile Samples From Patients With Biliary Strictures Related to Pancreatico-biliary Cancers

The differential diagnosis between benign and malignant bile duct strictures is a difficult and demanding task for clinicians. Clinical, biochemical, and radiological characteristics of malignant biliary strictures are non-specific and tissue diagnosis is difficult to obtain preoperatively. For this reason, there is a need for the development of new diagnostic modalities. Of particular interest is the quest of tumor markers secreted or shed in bile by tumor cells developing in the biliary tract.

In addition, patient's tumor molecular profile is the basis for selecting personalized therapy. Cholangiocarcinomas are characterized by a large genetic heterogeneity. The most frequent mutations are TP53, KRAS, BRAF, EGFR, MET, NRAS, PIK3CA, ERBB2, SMAD4, FBXW7, ARID1A, PBRM1, BAP1 et IDH1/2. In the case of pancreatic cancers, the most frequent are KRAS mutation detected in 90 % of the patients and CDKN2A, SMAD4, TGFBR1, TGFBR2, ATM, BRCA2, MLL2, MLL3, KDM6A, ARID1A, ARID1B, SMARC1, GNAS and RNF43 mutations.

It is well established that KRAS and P53 mutations can be detected in bile samples from patients with biliary strictures related to cholangiocarcinoma and cancer of the head of the pancreas. The main objective is to determine if bile sample analysis from patients with malignant biliary stricture may allow to identify tumor mutation profile and determine tumor genotype. A secondary objective is to evaluate the diagnostic value of Vascular Endothelial Growth Factor (VEGF) and metallo-proteinases (MMPs) levels in bile samples.

Tumor genotyping will be performed in bile samples (supernatant and cell pellet) and tumor tissues in a series of 10 patients surgically treated for malignant biliary stricture related to cholangiocarcinoma or cancer of the head of the pancreas. The biochemical markers, VEGF and MMPs, will be assessed in bile samples obtained during endoscopic retrograde cholangiopancreatography in 50 patients with malignant biliary stricture and 50 patients treated for benign biliary diseases.

Study Overview

• Status: Completed
• Conditions: Cholangiocarcinoma, Cancer of the Head of the Pancreas
• Intervention / Treatment: Biological: bile sample analysis; Biological: biochemical markers, VEGF and MMPs, in bile samples

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• France
  • Reims
    • France, Reims, France, 51092
      • CHU Reims

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with malignant biliary stricture and 50 patients with benign biliary diseases

Description

1. Tumor genotyping in bile samples:

   Inclusion criteria :

   • patients surgically treated for malignant biliary stricture related to cholangiocarcinoma or cancer of the head of the pancreas.
   • diagnosis of cholangiocarcinoma or cancer of the head of the pancreas confirmed by histopathological analysis of the resected specimen
   • adult patients

   Exclusion criteria :

   - patient who did not accept the storage of bile and tissue in the tissue Bank of Reims university hospital

2. Measurement of biochemical markers, VEGF and MMPs in bile samples obtained during endoscopic retrograde cholangiopancreatography in 50 patients with malignant biliary stricture and 50 patients treated for benign biliary diseases.

Inclusion criteria:

• patients with benign biliary diseases or malignant biliary stricture (cholangiocarcinoma or cancer of the head of the pancreas.
• indication of endoscopic retrograde cholangiopancreatography for diagnostic and therapeutic purposes
• adult patients Exclusion criteria
• patient who did not accept the storage of bile and tissue in the tissue Bank of Reims university hospital

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients with malignant biliary stricture	Biological: bile sample analysis; tumor mutation profile tumor genotype; Biological: biochemical markers, VEGF and MMPs, in bile samples
patients with benign biliary diseases	Biological: biochemical markers, VEGF and MMPs, in bile samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tumor genotyping	Day 0

Collaborators and Investigators

• Sponsor: CHU de Reims

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: September 2, 2016
• First Submitted That Met QC Criteria: September 2, 2016
• First Posted (Estimate): September 8, 2016

Study Record Updates

• Last Update Posted (Estimate): December 28, 2016
• Last Update Submitted That Met QC Criteria: December 27, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Cholangiocarcinoma
• Other Study ID Numbers: PA15117