A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
Status:
Completed
Trial end date:
2017-07-01
Target enrollment:
Participant gender:
Summary
Renal cell carcinoma (RCC) accounts for more than 200,000 new cases of cancer and over
100,000 cancer deaths annually in the World (Ferlay, et al., 2004). It is estimated that
there were about 15,000 new cases of RCC in the region that excludes the Americas, European
Union and Japan. Renal cell carcinomas arise from the proximal tubal epithelium are more
common in males than in females with an overall lifetime risk of 1 in 75 and a median age of
diagnosis of 65 years.
Everolimus (Certican®) has been approved since 2003 in more than 60 countries for the
prevention of organ rejection in patients with renal and cardiac transplantation. Everolimus
(RAD001) is a derivative of rapamycin, which acts as a signal transduction inhibitor. It
targets mTOR, a key protein kinase regulating cell growth, proliferation, and survival. The
mTOR pathway activity is modulated by the phosphatidylinositol-3-kinase (PI3K)/protein kinase
B AKT (AKT) pathway, a pathway known to be deregulated in numerous human cancers. RAD001
(Afinitor®) has been investigated as an anticancer agent based on its potential to act:
- directly on the tumor cells by inhibiting tumor cell growth and proliferation;
- indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent
inhibition of tumor cell hypoxia-inducible factor 1 (HIF-1) activity, VEGF production,
and VEGF-induced proliferation of endothelial cells).
Primary: To evaluate the PFS rate over time.
Secondary:
- To evaluate the disease control rate (stable disease [SD] + partial response [PR] +
complete response [CR]);
- To evaluate the objective response rate (ORR; where ORR = CR + PR) and duration;
- To describe the safety profile of RAD001.