Clinical trial NCT02499458: Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer
Official title: Prospective Validation of Circulating Tumor Cells (CTCs) and Circulating Endothelial Cells (CECs) as Prognostic Biomarkers in Clear Cell Renal Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Clear Cell Renal Cancer
Circulating Tumor Cells
Circulating Endothelial Cells
Prognostic Biomarkers
Predictive Biomarkers
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: London Health Sciences Centre
name: Hamilton Health Sciences Corporation
First posted: 2015-07-16
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Oncology care centre

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. ECOG performance status 0-2
2. Age over 18 years
3. Diagnosed renal cancer with clear cell histology
4. Metastatic disease
5. Predicted life expectancy over 2 months
6. Targeted treatment with an anti-VEGF or anti-mTOR agent as first or second line therapy
7. Standard imaging evaluation 4 weeks prior to inclusion
8. Planned for standard imaging within 16 weeks after start of therapy

Exclusion Criteria:

1. Presence of substantial comorbidities (uncontrolled heart or respiratory dysfunction, severe renal or hepatic impairment \[Cl Cr below 30ml/h OR Bb\>3X ULN\])
2. History of a malignancy other than non-melanoma skin cancer in the previous 5 years
3. Any other contraindication to targeted treatments.

Primary outcomes:
measure: Sensitivity/specificity of CTC enumeration (microfluidics vs CellSearch)
timeFrame: 24 months
measure: Progression free survival (PFS).
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 24 months
measure: Radiological response
timeFrame: within 16 weeks after start of study
measure: Molecular characterization of CTCs
timeFrame: baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)
measure: Enumeration of CECs
timeFrame: baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: London Health Sciences Centre
name: Alison L Allan, PhD
role: PRINCIPAL_INVESTIGATOR
References: