Renal Cancer Cell Clinical Trial
Official title:
Activity and Safety of Third Line Tyrosin Kinase Inhibitor (TKI) After 2 Tyrosin Kinase Inhibitors (TKIs) in Patients With Metastatic Renal Cell Carcinoma (mRCC) (Tokio Study)
The study aims to evaluate the efficacy of a third TKI after two previous lines of therapy
with TKIs, in terms of median progression free survival (mPFS), in patients affected by
metastatic renal cancer cell.
Patients receiving the sequence Sunitinib- Axitinib, will receive Sorafenib.
Patients receiving the sequence Pazopanib-Sorafenib, will receive Sunitinib.
Sorafenib dosage 400mg orally, twice a day.
Sunitinib dosage 50 mg 4 weeks on followed by 2 weeks a rest.
The therapy will be continued until disease progression or unacceptable toxicity.
Advanced RCC presents poor prognosis, because his pathogenesis is not clearly understood.
Additionally, the Von Hippel Lindau (VHL) gene is mutated in the majority of sporadic and
familial clear cell renal cancer. The mechanism by which VHL mutation leads to RCC
development and progression is postulate to be in part thought production of the protein VEGF
(Vascular Endothelial Grow Factor).
VEGF over-expression may be pertinent in RCC via multiple mechanism in addition to
angiogenesis, including effects on dendritic cells and inhibition of apoptosis through
preservation of cyclin dependent kinase inhibitors.
VEGF expression could represented an independent prognostic factors for survival possibly
linking expression of this protein with clinical outcome.
Sunitinib and pazopanib are the standard therapy as first line in mRCC. At sunitinib failure
a second line with axitinib or everolimus or sorafenib should be considered to improve the
clinical outcome of the disease. Up to now there is not a clear evidence of superiority in
favour of an agent versus the others available.
At pazopanib failure no evidences are available to support physicians in the decision making
in the everyday clinical practice.
Moreover no data are available in third line with a TKi after two previous lines of therapy
with TKIs.
This study was designed to evaluate prospectively the efficacy of two different sequences of
TKis in third line:
The first (group A) to evaluate the efficacy of sorafenib after two previous lines of TKIs
with sunitinib followed by axitinib
The second (group B) to evaluate the efficacy of sunitinib after two previous lines of TKIs
with pazopanib followed by sorafenib.
400 mg bid is the standard approved dose for sorafenib in the treatment of mRCC while 50 mg
for 4 consecutive weeks every six weeks is the standard dose for sunitinb
;