Enumeration of Circulating Tumour Cells (CTCs) in Patients With Advanced Solid Malignancy Using Complementary Metal Oxide Semiconductor (CMOS) Technology

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National University Hospital, Singapore
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01596452
First received: April 2, 2012
Last updated: December 8, 2013
Last verified: December 2013
  Purpose

Modern anti-cancer treatments are focused on development of molecular based therapies i.e. specific treatments targeted against underlying biological processes. There is still much to learn about the biology of cancer, especially in tumours such as colorectal and lung cancer where it is likely multiple heterogenous signaling pathways are responsible for progression of disease. This project aims to evaluate circulating tumour cells (CTCs) as a surrogate biomarker for tumour characteristics and to determine how they may used to identify new targets for therapeutic agents. Their use could be applied to diagnosis of cancer, prediction of response to therapies and prognosis, ultimately across a broad range of tumour types. Currently the only way to investigate molecular features of a cancer is through procurement of an invasive tumour biopsy that is often difficult to obtain, often results in insufficient material and is unpleasant for the patient. A blood-based test would provide a much more practical and patient friendly alternative. The enumeration and molecular characterisation of CTCs has the novel potential of being a "virtual biopsy" of the tumour and offers the opportunity for immediate therapeutic decisions (eg. if the tumour develops a therapy resistant genotype while on treatment). CTCs have been known to circulate in bloodstream of cancer patients for many years and are known to lead to cancer metastases. They have been very difficult to detect, up until recently, due to the complexity of the metastatic process and detecting relatively small numbers of CTCs amongst billions of red and white blood cells. However, technology has moved on dramatically in the last few years. The FDA approved CellSearch platform (Veridex, NJ) can isolate and enumerate CTCs based on the immunomagnetic capture of EpCAM (epithelial cell adhesion molecule) positive cells. Several studies have recently demonstrated the value of CTC enumeration in reflecting prognosis and predicting early response to systemic chemotherapy. For example, in a study comprising 456 patients with metastatic colorectal cancer starting a new line of therapy, patients with =3 CTCs per 7.5 ml blood at baseline had shorter progression free survival (PFS) and overall survival (OS) compared to those patients with < 3CTCs at baseline (PFS 4.5 versus 7.9 months P=0.0001; OS 8.5 versus 19.1 months P=0.0000 respectively). Overall survival for patients converting to or maintaining CTCs =3 within a few weeks of commencing systemic therapy remained worse than for those patients maintaining CTC counts < 3 per 7.5ml blood. Similar results have been reported in patients with breast and hormone refractory prostate cancer (HRPC). These studies have led to FDA approval of the CellSearch system as an adjunct to monitoring patients with these 3 tumour types. The CellSearch platform, however, does not allow for the downstream DNA analysis of captured cells and the ferroparticle-coated CTCs are non-viable. Furthermore, this platform is a multi-machine, multi-kit system that is laborious (typical 3-7 days turnover time), expensive (USD 650), and subject to operator variance. In this protocol, the investigators propose for the first time, an automated, fully quantitative system for isolation and enrichment of CTCs. The key differentiating feature of our novel CMOS system is the electrochemical identification and counting of tumour cells using a high density electrode array with associated electronics for addressing the electrodes. This leads to a standardized assay for tumour cells with a shorter turnover time and without the need of a skilled operator. This system also holds the potential for allowing the molecular characterization of CTCs. This study aims to enumerate CTCs using a novel CMOS technology in patients with metastatic cancer who are scheduled to receive palliative chemotherapy, and to correlate CTC number with clinical outcome. In Part I of the study, the investigators will recruit 10 patients with metastatic NSCLC and 10 patients with metastatic CRC in order to assess the feasibility of CTC enumeration in patients. In particular, the investigators aim to establish whether CTCs are detectable using the novel CMOS technology in patients with metastatic cancer. In Part II of the study, the investigators will recruit 21 patients with metastatic NSCLC and 89 patients with metastatic CRC in order to compare CTC counts as determined by the CMOS technology with CTC counts as determined by the CellSearch platform. Blood samples will be collected at a single time point prior to the start of palliative chemotherapy. CTC numbers will be correlated with clinical outcome in all evaluable patients.

The investigators hypothesize that CTC enumeration by a novel CMOS technology is non-inferior to CTC enumeration by the CellSearch platform in patients with advanced solid malignancies.


Condition
Non Small Cell Lung Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • Establish whether CTCs are detectable using novel CMOS technology in patients with metastatic cancer. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare CTC counts as determined by CMOS technology with CTC counts as determined by immunomagnetic capture with the CellSearch platform (Veridex, NJ). [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Determine the relationship between baseline CTC number as determined by CMOS technology and clinical outcome. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 31
Study Start Date: June 2012
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients being treated for cancer at the National University Hospital (NUH), Singapore

Criteria

Inclusion Criteria:

  1. Patients with a diagnosis of either metastatic NSCLC or metastatic CRC are eligible.
  2. Patients should be due to undergo palliative chemotherapy as part of their standard clinical care.
  3. Patients must be able to receive and understand verbal and written information regarding the study and give written, informed consent.

Exclusion Criteria:

  1. Persons under 18 years of age.
  2. Conditions in which research blood sampling may increase risk of complications for the patient and/or the investigators. For example, uncontrolled bleeding, patients with a known blood-borne viral infection (eg. hepatitis B or C, HIV) or poor venous access.
  3. Other persons in whom clinical judgement by the investigator concluded that the patient should not participate in the study. For example, anticipated poor compliance to attend for follow-up.
  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: NCT01596452

Contacts
Contact: Ying Kiat Zee, MBBS, MRCP +65 6779 5555 Ying_Kiat_Zee@nuhs.edu.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore
Contact: Ying Kiat Zee, MBBS, MRCP    +65 6779 5555    Ying_Kiat_Zee@nuhs.edu.sg   
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Ying Kiat Zee, MBBS, MRCP National University Hospital, Singapore
  More Information

Publications:
Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01596452     History of Changes
Other Study ID Numbers: Version 1
Study First Received: April 2, 2012
Last Updated: December 8, 2013
Health Authority: Singapore: Domain Specific Review Boards

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 22, 2014