Wyeth Pharmaceuticals, a division of Wyeth announced the initiation of the INTORACT (INvestigation of Torisel and Avastin Combination Therapy) study.
A worldwide randomized, open-label, phase IIIb study comparing Torisel (temsirolimus) plus Avastin (bevacizumab) versus Avastin plus interferon-alfa for first-line treatment of patients with advanced renal cell carcinoma (RCC). Wyeth Research is conducting the Intoract study with the support and assistance of Roche and Genentech.
"Several therapies have been introduced in the past few years that have led to improvements in the way we treat advanced kidney cancer," says Joseph S Camardo, MD, senior vice president, global medical affairs, Wyeth Pharmaceuticals. "In the INTORACT study, we hope to learn more about whether combining Torisel with other agents in the first-line setting may further improve outcomes for patients with this devastating disease".
The primary end point of the INTORACT study is independently assessed progression-free survival (PFS) of patients in all risk groups. Secondary end points include safety, investigator-assessed PFS, independently assessed objective response rate (complete response plus partial response) and overall survival.
A treatment regimen combining the mTOR (mammalian target of rapamycin) inhibitor Torisel with the vascular endothelial growth factor (VEGF) inhibitor Avastin was shown in a phase 1/2 trial of patients with stage IV renal cancer to have an acceptable safety profile and supported further investigation in a phase III study.
"We hope to learn whether a regimen that combines the angiogenesis inhibition of bevacizumab with the mTOR inhibition of temsirolimus may provide further evidence of clinical utility in advanced RCC," says Brian Rini, MD, of the Cleveland Clinic Taussig Cancer Institute in Cleveland, and co-principal investigator of Intoract.
RCC will account for approximately 85 per cent of the estimated 54,390 new cases of kidney cancer that will be diagnosed in the United States annually, and about 40 per cent of these patients will have advanced disease at the time of diagnosis. Clear-cell RCC accounts for about 75 per cent of all RCC cases.
Wyeth is conducting a number of studies examining Torisel in various settings.
Torisel is the only approved cancer therapy that specifically inhibits the mTOR kinase, an important regulator of cell proliferation, cell growth and cell survival. Inhibition of mTOR in treated cancer cells blocked the translation of genes that regulate the cell cycle. In vitro studies using renal cancer cell lines, Torisel inhibited the activity of mTOR and resulted in reduced levels of certain cell growth factors involved in the development of new blood vessels, such as vascular endothelial growth factor.