Cancer Stem Cell Markers and Prognostic Markers in Circulating Tumor Cells

Metastatic colorectal cancer (mCRC) has a five year survival of <10% and is the cause of
death of nearly 50,000 individuals in the United States each year. Current first and second
line therapies for mCRC include FOLFOX, XELOX, or FOLFIRI in combination with Bevacizumab or
Cetuximab or Panitumumab, as well as Xeloda, camptosar or infusional 5-FU within various less
intensive regimens for patients who cannot tolerate full-dose chemotherapy. Current practice
involves evaluation of response by imaging at 2-3 months after initiation of therapy. Recent
studies have demonstrated that the number of circulating tumor cells (CTCs) in the blood of
patients with mCRC has independent prognostic value in terms of reflecting disease burden as
well as indicating response to therapy. The use of CTC counts offers the possibility of
predicting response in treated patients at an earlier time than through standard means by
using CT scans. The investigators hypothesize that subsets of CTCs with cancer stem cell
(CSC) markers or other known prognostic markers may improve the prognostic value of CTC
evaluation in the course of therapy of patients with mCRC. The protocol will use Veridex
CellSearch technology and will when possible compare this to other emerging technologies
including microfluidic devices that can isolate CTCs or GFP-expressing adenoviruses that
replicate in telomerase-expressing epithelial tumor cells ex-vivo. The protocol will enroll
200 patients with metastatic colorectal cancer receiving therapy. Additional proposed
laboratory studies may unravel important biological insights into the relationship of CTC
genomic and genetic profiles as they compare to the primary tumors. Additionally the
investigators hope to gain an understanding of potential subgroups of patients that have very
high numbers of CTCs or those with early relapse of CTC after early reduction of CTC numbers.
The impact of this research may be in better prediction of response to mCRC therapy so that
patients can be treated with second line or other experimental therapy if they are unlikely
to respond to their current therapy as predicted by CTC evaluation.

Inclusion Criteria:

- Patients with the diagnosis of metastatic colorectal cancer, either newly diagnosed or
recurrent, with measurable disease that has not been irradiated within the last 5
weeks.

- Age > 18 years old

- ECOG performance status 0-3

Exclusion Criteria:

- Patients who have received prior therapy in the last 5 weeks

- Ongoing therapy with a particular regimen that was initiated prior to enrollment and
lack of availability of baseline CTC evaluation

- Patient with concurrent diagnosis of other active solid malignancies will be exclude

- Patient life expectancy of less than six weeks