NCT03456401

Third Line TKI After 2 TKIs in Patients With mRCC (Tokio Study)

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)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

Conditions

• Renal Cancer Cell

Interventions

Type	Name	Description
DRUG	Sorafenib or Sunitinib	After two lines of TKIs, patients received a third line with sunitinib or sorafenib, according to previous treatments

Timeline

• Start date: 2014-11-01
• Primary completion: 2017-11-08
• Completion: 2017-11-08
• First posted: 2018-03-07
• Last updated: 2018-03-07

Locations

1 site across 1 country: Italy