Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma

• Time to progression [ Time Frame: Time from beginning of therapy until disease progression or death ] [ Designated as safety issue: No ]
  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.
  
  

• Overall survival [ Time Frame: Time from randomization until death ] [ Designated as safety issue: No ]
  For all subjects who have not died at the time of statistical analysis, duration of survival will be censored at the date of last contact. Kaplan-Meier methodology will be used to estimate the magnitude of the treatment effect as described for progression-free survival.
  
  
• Rate of objective responses, complete responses or partial responses, evaluated by RECIST criteria. [ Time Frame: Two consecutive occasions 4 weeks or more apart ] [ Designated as safety issue: No ]
  A complete or partial response determined on two consecutive occasions 4 weeks or more apart by the investigator using RECIST. Subjects without a post-baseline tumor assessment will be considered non-responders. An estimate of the objective response rate together with 95% confidence intervals will be calculated
  
  
• Rate of grade 3 and 4 non-hematologic and grade 4 hematologic NCI-CTCAE toxicity. [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
  All grade 3 and 4 adverse events, serious adverse events, and adverse events leading to study treatment interruption or discontinuation will be recorded. Verbatim descriptions of treatment-emergent adverse events will be coded to thesaurus terms. All grade 3 and 4 adverse events, serious adverse events and adverse events leading to study treatment interruption or discontinuation will be summarized according to treatment arm and NCI Common Toxicity Criteria for Adverse Effects (CTCAE) grade. For each subject's adverse events, the maximum severity achieved will be used in the summaries.
  
  

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