Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma

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.

The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer.

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

Inclusion Criteria:

• Signed informed consent to participate in this study.
• Histological diagnosis of renal cell carcinoma.
• Age greater or equal 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance status of 2 or better.
• Life expectancy of at least 3 months.
• Failure or intolerance to previous treatment with Sutent® and/or Nexavar®.
• Most recent systemic treatment at least 1 month from the beginning of treatment.
• Most recent local treatment (surgery or irradiation) > 2 weeks from the beginning of treatment.
• At least one site of measurable disease by CT scan or MRI (RECIST criteria).
• Baseline hemoglobin >9 g/dl, platelets > 100,000/mm3, absolute neutrophil count (ANC >1500/mm3.

Exclusion Criteria:

• Previous treatment with Tarceva™, Iressa™, Rapamune™, temsirolimus or everolimus.
• Untreated metastasis to the central nervous system.
• Previous solid organ, bone marrow or stem-cell transplant.
• Known AIDS or HIV infection.
• Symptomatic or poorly controlled chronic heart failure.
• Chronic renal failure requiring dialysis on a regular basis.
• Chronic liver failure.
• Serum aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), alkaline phosphatase or bilirubin >1.5 x the upper limit of normal for the local laboratory.
• Pregnant or breast-feeding women.
• Other invasive malignant diseases within 5 years (other than squamous or basal cell carcinoma of the skin).
• Inability to provide informed consent
• Any other serious and/or unstable medical, psychiatric, or other condition considered by the P.I. to preclude safe or reasonably compliant participation in the protocol.