Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Sunitinib

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Sorafenib will be administered at 400 mg bid daily Sunitinib will be administered at 50 mg die orally (4 week on/2 weeks off)

After two lines of TKIs, patients received a third line with sunitinib or sorafenib, according to previous treatments

Sorafenib or Sunitinib

Giuseppe Procopio, MD

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

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)

To evaluate the efficacy of a third TKI after two previous lines of therapy with TKIs, in terms of mPFS; time from the first treatment administration to first disease progression or death (months). It will be evaluated up to five years.

To evaluate overall survival: time from first treatment to death (months) (up to five years).

To evaluate the safety of a third line TKI; it will be evaluated and graded according to NCI-CTC version 3.0 criteria (Common Toxicity Criteria). Adverse events will be registered since treatment starts until end of treatment visit (30 +/- 7 days after end of treatment)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Third Line TKI After 2 TKIs in Patients With mRCC (Tokio Study)	NCT03456401	Renal Cancer Ce...	Sorafenib or Su...	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Third Line TKI After 2 TKIs in Patients With mRCC (Tokio Study)	NCT03456401	Renal Cancer Ce...	Sorafenib or Su...	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for renal cancer cell