Prospective Validation of Circulating Tumor Cells (CTCs) and Circulating Endothelial Cells (CECs) as Prognostic Biomarkers in Clear Cell Renal Cancer

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Prospective Validation of Circulating Tumor Cells (CTCs) and Circulating Endothelial Cells (CECs) as Prognostic Biomarkers in Clear Cell Renal Cancer

Condition: Clear Cell Renal Cancer, Circulating Tumor Cells, Circulating Endothelial Cells, Prognostic Biomarkers, Predictive Biomarkers

Intervention:

  • Other: None- observational study

Purpose: 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 Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02499458

Sponsor: Lawson Health Research Institute

Primary Outcome Measures:

  • Measure: Sensitivity/specificity of CTC enumeration (microfluidics vs CellSearch)
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Progression free survival (PFS).
  • Time Frame: 24 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Overall survival (OS)
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Radiological response
  • Time Frame: within 16 weeks after start of study
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:
  • Measure: 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)
  • Safety Issue:

Estimated Enrollment: 70

Study Start Date: November 2014

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Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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.

Contact:

  • Alison L Allan, PhD
  • 519-685-8600 Ext. 55134

Location:

  • London Health Sciences Centre
  • London Ontario N6K 4L6 Canada

View trial on ClinicalTrials.gov

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