Clinical Trial: Erlotinib for Chemoprevention in Trisomy 7 Positive Primary Sclerosing Cholangitis (PSC)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open Label Pilot Trial of Erlotinib (Tarceva) in Primary Sclerosing Cholangitis With Trisomy 7

Brief Summary:

Primary sclerosing cholangitis (PSC) is a chronic inflammatory condition of the bile ducts of unknown etiology. It is characterized by diffuse inflammation and stricturing of the entire biliary tree, eventually resulting in cirrhosis of the liver. Patients with PSC are at increased risk for the development of cholangiocarcinoma (CCA), a cancer arising from bile duct epithelium. This risk is estimated to be approximately 1 to 1.5% per year. It is postulated that chronic inflammatory changes in the biliary epithelium promote CCA formation. The prognosis of CCA is fatal. The only potentially curative therapy is surgical; however, only a minority of patients qualify for surgical treatment.

Several studies have demonstrated overexpression of the epidermal growth factor receptor (EGFR) in CCA cells. EGFR is a type 1 tyrosine kinase promoting cell proliferation, migration and altered cell adhesion - typical characteristics of malignant neoplasias. In CCA cells, EGFR-activation is sustained resulting in cancer progression. In human CCA samples, EGFR-expression correlates with higher histologic grade, poor prognosis, and risk of recurrence. The EGFR gene is located on the short arm of chromosome 7 (7p12). Chromosomal abnormalities of the bile duct epithelium, particularly trisomy 7 (i.e. three copies of chromosome 7) can be detected in biliary epithelial samples obtained by endoscopic retrograde cholangiopancreatography (ERCP) in PSC patients. The finding of cells with trisomy 7 has preceded the development of aneuploidy and multiple chromosomal abnormalities in a number of patients, the latter chromosomal abnormalities are characteristic of CCA. Trisomy 7 amplifies the gene for EGFR thereby presumably promoting overexpression of this growth factor receptor. In a cohort of patients with Trisomy 7 and Primary Sclerosing Cholangitis patients followed for 1 year, the rate of developm

Detailed Summary:
Sponsor: Mayo Clinic

Current Primary Outcome: To examine the safety and tolerability of Tarceva (Erlotinib) in patients with primary sclerosing cholangitis and trisomy 7 on biliary cytology. [ Time Frame: 6 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome: To assess among patients with primary sclerosing cholangitis and trisomy 7 the resolution of this cytologic abnormality following treatment with Tarceva (Erlotinib). [ Time Frame: 6 months ]

Original Secondary Outcome: Same as current

Information By: Mayo Clinic

Dates:
Date Received: August 5, 2009
Date Started: August 2009
Date Completion:
Last Updated: January 9, 2014
Last Verified: January 2014