Cancer Stem Cell Markers and Prognostic Markers in Circulating Tumor Cells

Prevalence of Stem Cell and Prognostic Markers in Circulating Tumor Cells of Patients With Metastatic Colorectal Cancer Undergoing Chemotherapy

The study will enroll patients with metastatic colorectal cancer receiving chemotherapy. A total of approximately 22 cc of blood will be drawn during various chemotherapy infusions. Additional proposed laboratory studies may unravel important biological insights into the relationship of circulating tumor cell 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 circulating tumor cells or those with early relapse of circulating tumor cells after early reduction of circulating tumor cell numbers.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center

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 metastatic colorectal cancer

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Blood draws; Laboratory studies will be performed at baseline; Cycle 1, Day 1; Cycle 1, Day 7; Cycle 2, Day 1; Cycle 3, Day 1; Cycle 4, Day 1; Cycle 6, Day 1; Cycle 12, Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary endpoint: correlation of stem cell markers on CTCs with response to therapy	Correlate the presence of stem cell markers and prognostic markers on circulating tumor cells with response to therapy for advanced colorectal cancer, as well as overall survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome: Correlation of stem cell markers in primary tumors with stem cell markers in CTCs	Evaluate the primary tumor if available for stem cell markers and prognostic markers. Perform genomic analysis of CTC DNA. Compare genomic analysis of primary tumor and CTC DNA. Evaluate CTC gene expression profiles and compare with primary tumor profiles. Evaluate emerging microfluidic devices in pilot studies that use drops of blood for CTC analysis.	3 years

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Wafik S El-Deiry, MD, PhD, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Publications and helpful links

General Publications

• Allen JE, El-Deiry WS. Circulating Tumor Cells and Colorectal Cancer. Curr Colorectal Cancer Rep. 2010 Oct 1;6(4):212-220. doi: 10.1007/s11888-010-0069-7.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: January 28, 2011
• First Submitted That Met QC Criteria: January 28, 2011
• First Posted (Estimate): January 31, 2011

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: colorectal cancer; circulating tumor cells; metastatic colorectal cancer; advanced colorectal cancer; tumor microenvironment; prognostic markers; stem cell markers
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Neoplasm Metastasis; Colorectal Neoplasms; Neoplastic Cells, Circulating
• Other Study ID Numbers: PSHCI 10-066; PSHMC IRB No. 34902EP (Other Identifier: Penn State Hershey Medical Center IRB No. 34902EP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: To evaluate if data is valuable