NCT03097601: SUNITRES

ELR+CXCL Cytokines in Metastatic Kidney Cancers: Predictive Markers of Resistance to Sunitinib

Completed Last updated 21 July 2020

What this trial tests

trial testing ELR+CXCL cytokines levels are of sunitinib response in Metastatic Kidney Cancers in 60 participants. Completed in 30 December 2019.

Timeline

2 June 2016

Primary endpoint
30 December 2019

30 December 2019

Quick facts

Lead sponsor	Centre Antoine Lacassagne
Status	Completed
Study type	OBSERVATIONAL
Enrollment	60
Start date	2 June 2016
Primary completion	30 December 2019
Estimated completion	30 December 2019
Sites	1 location across France

Drugs / interventions tested

• ELR+CXCL cytokines levels are of sunitinib response

Conditions studied

• Metastatic Kidney Cancers — all drugs for Metastatic Kidney Cancers →

Sponsor

Centre Antoine Lacassagne — full company profile →

Who can join

18 and older, any sex, with Metastatic Kidney Cancers. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.