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

Digestive System Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Anti-Infective Agents

Amino Acids

Everolimus

Imatinib Mesylate

Erlotinib Hydrochloride

Gefitinib

Sirolimus

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

Tyrosine Kinase Inhibitors

Tyrosine

Erlotinib 150 mg tablet or Gefitinib 250 mg tablet by mouth every day

Everolimus 10 mg orally once daily every day

Sorafenib 400 mg twice a day at least one hour before or two hours after eating or Sunitinib 50 mg orally once a day

No intervention was performed for patients without any gene alternation or without any available target agents

Erlotinib 150mg talbet or Gefitinib 250 mg tablet per day for patients with EGFR gene alternation

Erlotinib or Gefitinib

Everolimus 10 mg orally once daily every day for patients with mTOR gene alternation

Imatinib 400 mg tablet orally per day for patietns with KIT, PDGFR, ABL gene alternation

Imatinib

Sorafenib 400 mg twice a day at least one hour before or two hours after eating or Sunitinib 50 mg orally once a day with or without food for patients with VEGFR, KIT, RAF gene alternation

Vandetanib 300 mg orally once daily for patients with RET gene fusion.

Vandetanib

Yanghong Deng, PhD

Yanhong Deng, PhD

Hypothesis: Different patients have different biomarkers, if doctors know about the biomarkers of patients; they may be able to prescribe a regimen that is better suited to the patient's specific needs. This is a pilot study. Here, we used whole exon sequencing and Integrated genomic network analysis to identify the biomarker or gene. We aimed to learn if the drug chosen based on biomarkers can help to control metastatic gastrointestinal cancer who had failed from all standard and available regimens.

Rational: Cancer sequencing (CS) promises to become the centerpiece of personalized oncology by informing on treatments targeted to each tumor's unique genetic constitution. This data can be critical to making an informed decision for disease management, though this may not be the case for all patients. CS identifies variations or differences in the DNA and/or RNA of the cells in an individual's tumor by comparison to that of his/her normal cells. These somatic variations may, on further interpretation, be identified as key drivers of carcinogenesis. Such information may predict a patient's prognosis, response to currently available treatments or prompt the development of novel therapeutics. Though CS has the potential to personalize and optimize cancer care, it may produce a vast amount of data and unique changes in the DNA/RNA that may be difficult to interpret at the present time.

Using the Integrated genomic network analysis, we could have better understanding of the underlying processes and pathways involved in tumor onset and progression. And then we could choose a specific treatment regimen and develop personalized cancer therapies

A Pilot Study of Genomic Sequencing Guided Individualized Therapy in Gastrointestinal Cancers, GITIC Study

A Pilot Study of Genomic Sequencing Guided Individualized Therapy in Gastrointestinal Cancers

The disease control rate of all patients.

From the date of enrollment until the date of death from any cause.

After identifying the driver gene and choosing the specific target drug, the response rate of all patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
A Pilot Study of Genomic Sequencing Guided Individualized Therapy in Gastrointestinal Cancers, GITIC Study	NCT02013089	Gastrointestina...	Erlotinib or Ge... Everolimus Imatinib Sorafenib or Su... Vandetanib	18 Years - 70 Years	Sun Yat-sen University
A Pilot Study of Genomic Sequencing Guided Individualized Therapy in Gastrointestinal Cancers, GITIC Study	NCT02013089	Gastrointestina...	Erlotinib or Ge... Everolimus Imatinib Sorafenib or Su... Vandetanib	18 Years - 70 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for sorafenib or sunitinib