A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™ (Erlotinib Hydrochloride) and Rapamune™ (Sirolimus) in the Treatment of Metastatic Renal Cell Carcinoma.
Despite recent advances metastatic renal cell carcinoma remains an incurable condition.
Currently available treatment with high-dose interleukin-2 can lead to complete responses in
a small minority of selected patients but is markedly toxic and not broadly available.
FDA-approved multikinase inhibitors (sorafenib and sunitinib malate) often cause partial and
transient tumor regression. There is no standard treatment metastatic renal cell carcinoma
for patients whose disease progressed on multikinase inhibitors. The kinase mammalian target
of rapamycin (mTOR) is overstimulated in a subset of renal cell carcinomas and other
malignancies and can be blocked by sirolimus leading to growth arrest. Erlotinib
hydrochloride is a drug that blocks the function of the epidermal growth factor receptor
(EGFR), often over expressed in kidney cancer. Sirolimus and EGFR inhibitors and been safely
used in combination. In vitro experiments show that erlotinib enhances the sirolimus induced
growth impairment in a panel of renal cell carcinoma cells. In the present study patients
with metastatic renal cell carcinoma whose disease progressed on multikinase inhibitors will
be treated with the combination of erlotinib hydrochloride (Tarceva™) and sirolimus
(Rapamune™). This is a single arm trial with no placebo or drug-based control arm
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to progression
Time to progression is defined as the time from beginning of therapy until disease progression or death. For subjects who have not progressed at the time of statistical analysis, progression-free survival will be censored at the date of their last tumor assessment. Kaplan-Meier methods will be used to estimate median progression-free survival.
Time from beginning of therapy until disease progression or death
Thomas W Flaig, MD
University of Colorado, Denver
United States: Food and Drug Administration
|University of Colorado Hospital||Denver, Colorado 80262|