Last updated on June 2018

A BIOmarker Driven Trial With Nivolumab and Ipilimumab or VEGFR tKi in Na ve Metastatic Kidney Cancer


Brief description of study

Disease and Stage: nave metastatic kidney cancer.

A multicenter, randomized, a Phase 2 BIOmarker driven trial with Nivolumab and Ipilimumab or VEGFR tKi in nave metastatic Kidney cancer

Detailed Study Description

Research Hypothesis: Molecular groups of ccrcc will define patients who will respond to nivolumab alone, nivolumab combined with ipilimumab, or VEGFR-TKI (sunitinib or pazopanib) in subjects with previously untreated metastatic renal cell carcinoma (mRCC).

Conditions
  • Advanced or metastatic RCC: previously untreated in metastatic setting.
  • Frozen tumor samples available for molecular group determination.
  • Determination of molecular subgroup prior to randomization.

Product(s):

  • Nivolumab administered IV over 60 minutes at 3 mg/kg combined with ipilimumab administered IV over 30 minutes at 1 mg/kg every 3 weeks for 4 doses followed by nivolumab administered IV over 60 minutes at 3 mg/kg every 2 weeks or nivolumab a l o n e administered IV over 60 minutes at 3 mg/kg every 2 weeks (molecular group 1 and 4), or TKI (molecular group 2 and 3), pazopanib or sunitinib according to investigator's choice until disease progression, unacceptable toxicity or other reasons specified in the protocol.

Biological assessments:

Molecular groups (1 to 4) will be determined for all patients from frozen tumor tissue samples or from fresh tumor samples immediately stored in "RNA later" medium.

Further exploratory biological assessments will be performed in order to define predictive biomarkers of response to N+I, N alone or TKI (sunitinib or pazopanib) by analyzing tumor specimens and blood samples:

  • To assess gene expression of immune population markers in the primary tumor as well as in the metastases before beginning treatment, and at progression if safely achievable.
  • Gene expression analysis will be performed from frozen and FFPE tumor tissue in order to compare the two methods.
  • To assess the density and phenotype of selected immune populations (CD8, CD3/CD20, PD-1, TIM-3, LAG3, FoxP3) as well as the phenotype of tumor cells (PD-L1, PD-L2) by immunohistochemistry (IHC) in the primary tumor and metastases, before treatment initiation and at progression if safely achievable.
  • To assess the functional status of peripheral blood lymphocytes (PBL) by flow cytometry, before treatment initiation, during treatment, and at progression.
  • To quantify plasmatic angiogenesis-related (i.e. VEGF-A, VEGF-C its soluble receptors VEGFR-1 and 2 and co-receptors neuropilin 1 and 2, angiopoietins, SDF-1, PDGFs)) and endothelial cell-derived molecules (i.e. endoglin, VE-cadherin) before treatment initiation, during treatment, and at progression.
  • To correlate plasmatic angiogenesis-related molecules with tumor vascularization studied by immunofluorescence (IF) and a multi-spectral analyzer (Vectra technology) on tumor tissue.
  • To investigate a predictive role of the response of CXCL7 and sCD146 to TKI, nivolumab and/or nivolumab+ipilimumab.

Statistical Considerations:

An adaptative design will be used to ensure that conclusions can be made with a limited number of patients in each molecular group, which is the major constraint of the study.

Sample Size: Approximately 150 patients are planned to be treated. Given an expected failure rate of molecular grouping of less than 20%, 180 patients must be included.

Clinical Study Identifier: NCT02960906

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