- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02499458
Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer
December 20, 2019 updated by: Alison Allan, Lawson Health Research Institute
Prospective Validation of Circulating Tumor Cells (CTCs) and Circulating Endothelial Cells (CECs) as Prognostic Biomarkers in Clear Cell Renal Cancer
Circulating tumor cells (CTCs) have prognostic value in several tumor types, and increasing evidence suggests that molecular characterization of CTCs can serve as a "liquid biopsy" to understand and address treatment resistance.
The goal of this proposal is to demonstrate that CTCs can be accurately enumerated and characterized in metastatic clear cell renal cancer (CCRC) and can serve as prognostic/predictive biomarkers to improve treatment.
The challenge surrounding CTC analysis in CCRC is that most CTC technologies (including the clinical gold-standard CellSearch®) depend in epithelial markers such as EpCAM that are expressed at low or heterogeneous levels in CCRC.
Members of the research team have developed a novel CTC microfluidic technology that can effectively detect CTCs that are completely undetectable by CellSearch® because of very low EpCAM expression, as well as allowing for CTC recovery for downstream molecular characterization.
The goal of this proposal is therefore to test the hypotheses that (1) The microfluidics CTC technology will have better sensitivity/specificity relative to the CellSearch in metastatic CCRC; and (2) Enumeration of CTCs in metastatic CCRC patients (n=66) will have prognostic value, while molecular characterization of CTCs for expression of biomarkers (VHL, VEGF, mTOR, HIF1/HIF2, AKT) related to CCRC etiology will be predictive of response/resistance to targeted therapies.
Although CCRC is relatively uncommon, the lack of established adjuvant treatments and high cost of targeted therapies in the palliative setting makes the search for new prognostic/predictive biomarkers an important clinical goal.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Observational
Enrollment (Actual)
44
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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London, Ontario, Canada, N6K 4L6
- London Health Sciences Centre
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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
Oncology care centre
Description
Inclusion Criteria:
- ECOG performance status 0-2
- Age over 18 years
- Diagnosed renal cancer with clear cell histology
- Metastatic disease
- Predicted life expectancy over 2 months
- Targeted treatment with an anti-VEGF or anti-mTOR agent as first or second line therapy
- Standard imaging evaluation 4 weeks prior to inclusion
- Planned for standard imaging within 16 weeks after start of therapy
Exclusion Criteria:
- Presence of substantial comorbidities (uncontrolled heart or respiratory dysfunction, severe renal or hepatic impairment [Cl Cr below 30ml/h OR Bb>3X ULN])
- History of a malignancy other than non-melanoma skin cancer in the previous 5 years
- Any other contraindication to targeted treatments.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sensitivity/specificity of CTC enumeration (microfluidics vs CellSearch)
Time Frame: 24 months
|
For comparison of the 2 CTC platforms, a Bland-Altman plot will be constructed.
This plot is superior to standard correlation statistics in that it assesses agreement rather than association.
Initially we will use a Chi-Square test to compare the 2 methods at a cutoff point of ≥5 versus <5 CTCs/7.5mL, with simple comparison of PFS at this level.
As the cut-off point may not be the same for each method, we will also compare the methods using simple 2X2 contingency tables.
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24 months
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Progression free survival (PFS).
Time Frame: 24 months
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Survival analysis will be performed by Kaplan Meier and significance analysis will use the log-rank test.
Cox multivariate analysis will be performed to look at the number and molecular characteristics of CTCs as independent prognostic parameters of survival.
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24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: 24 months
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Survival analysis will be performed by Kaplan Meier and significance analysis will use the log-rank test.
Cox multivariate analysis will be performed to look at the number and molecular characteristics of CTCs as independent prognostic parameters of survival.
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24 months
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Radiological response
Time Frame: within 16 weeks after start of study
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Radiological assessment of disease status will be carried out as standard-of-care and subjected to correlative analysis relative to CTC status, PFS and OS.
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within 16 weeks after start of study
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Molecular characterization of CTCs
Time Frame: baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)
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CTCs will be recovered from the microfluidics device and subjected to molecular characterization for expression of markers related to angiogenesis and hypoxia.
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baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)
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Enumeration of CECs
Time Frame: baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)
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CTCs will be enumerated on both the CellSearch and the novel microfluidic device.
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baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Alison L Allan, PhD, London Health Sciences Centre
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2014
Primary Completion (Actual)
December 1, 2018
Study Completion (Actual)
December 1, 2018
Study Registration Dates
First Submitted
July 10, 2015
First Submitted That Met QC Criteria
July 14, 2015
First Posted (Estimate)
July 16, 2015
Study Record Updates
Last Update Posted (Actual)
December 24, 2019
Last Update Submitted That Met QC Criteria
December 20, 2019
Last Verified
December 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Neoplastic Processes
- Neoplasm Metastasis
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Neoplastic Cells, Circulating
Other Study ID Numbers
- 105484
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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