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Showing 1-5 of 5 trials
NCT06364631
Systemic therapy for renal cell carcinoma (RCC) relies on 2 classes of agents: anti-angiogenic targeted therapy (Vascular endothelial growth factor Tyrosine Kinase Inhibitor- VEGFR TKI) and immune checkpoint inhibitor (ICI), targeting either PD1/PDL1 axis or CTLA4. Combination therapy is SOC for clear cell RCC in all guidelines with either ICI-ICI or ICI-VEGFR TKI. However, no head-to-head comparison have been performed between the 2 approaches and patients are treated based on physician decision without clinical /biomarker factors to guide treatment selection. PDL1 staining is, to date, the biomarker that has demonstrated its ability to enrich for overall survival benefit favoring ICI-ICI strategy in PDL1(+) and ICI-VEGFR TKI in PDL1(-) patients. Study design has been developed to demonstrate that ICI-ICI is superior to ICI-VEGFR TKI in prolonging Overall Survival (OS) for PDL1(+) patients and to demonstrate that ICI-VEGFR TKI is superior to ICI-ICI in prolonging Progression Free Survival (PFS) and OS for PDL1(-) patients.
NCT02035358
In this Phase 1 Trial investigators plan to establish the MTD of HyperAcute®-Renal (HAR) immunotherapy in subjects with clinically metastatic renal cell carcinoma.
NCT03097601
Metastatic renal cell carcinomas (mRCC) are highly angiogenic tumors because of mutation of the pVHL gene leading to over-expression of VEGF. Therefore, mRCC represent a paradigm for the use of anti-angiogenic treatments targeting the VEGF/VEGFR pathway. Despite an increase of the time to progression these treatments, taken alone, are not curative with ineluctable progression especially for the reference treatment sunitinib a multi kinase inhibitors of VEGF, PDGF, CSF1 receptors and c-kit, FLT3 and RET. At progression on sunitinib, patients received mTOR inhibitors which is responsible, at least, of HIF1A mRNA translation, then on a third line sorafenib that inhibits VEGFR2, 3 PDGFR, c-KIT and B-RAF. The access to these different lines of treatment has finally prolonged survival but this situation is not satisfactory. Unexpected aspect associated with the use of anti-angiogenesis treatments was the diversity of the patients' response. Some patients are right away refractory and die rapidly, but the majority of patient has a transient response then progress and a few percentages of them are responder for a very long period of time. By only targeting normal endothelial cells and tumor neo-vascularization, the response should have been more homogenous, thus highlighting that the treatment induced a "Darwinian" adaptation of tumor cells and cells of the microenvironment. Two conclusions follow from these observations: 1- The need to identify predictive markers of efficacy; 2-The identification of druggable targets participating in progression on anti-angiogenic treatments. Our results have highlighted the ELR+CXCL cytokines, pro-inflammatory and pro-angiogenic cytokines as prognosis markers of survival of mRCC patients and relevant therapeutic targets on experimental tumors in mice. As VEGF/VEGFR, these cytokines are produced by tumor, endothelial and inflammatory cells. Their receptors (CXCR1, 2) are expressed physiologically by immune and endothelial cells and aberrantly by tumor cells generating at the same time autocrine proliferation loops, chronic angiogenesis and inflammation. Therefore, the CXCL/CXCR1,2 axis constitutes an independent axis of cancer development and propagation. However, the current standard of care is to administer anti-angiogenic therapies as the first line treatment. The objective of this project is linked to the identification of potent predictive markers of efficacy, easily measured in plasma samples. Deciphering the molecular mechanisms associated with the production of such cytokines by tumor cells and by cells of the microenvironment represents an interesting intellectual challenge and a relevant way to improve the current treatments by targeting, at progression on the current standard of care, other pathways than the VEGF/VEGFR axis.
NCT03846128
Patients treated on the first line of Sunitinib-targeted therapy for metastatic kidney cancer. Collection of additional blood tubes during routine blood tests for patient follow-up, to evaluate the plasma concentration of Sunitinib and its active metabolite desethyl-Sunitinib (DES)
NCT01336231
Longitudinal study nonrandomized, multicenter observational descriptive monitoring patients treated with anti-angiogenic for metastatic kidney cancer