Study of Pegylated Alfa Interferon, Sunitinib and Tarceva in Patients With Metastatic RCC

Inclusion Criteria:

* Histologically or cytologically confirmed metastatic or unresectable RCC. Patients must have a component of conventional clear cell renal carcinoma or papillary renal carcinoma.
* No more than three prior systemic therapies of any kind for RCC including: 1) Immunotherapy (Adjuvant vaccines, Interleukin-2, Interferon-α) 2) Chemotherapy 3) Molecular targeted agents (Nexavar \[Sorafenib\], Bevacizumab \[Avastin\]) 4) Investigational therapy
* Patients with their primary tumor in place who are appropriate surgical candidates should be strongly encouraged (but not required) to undergo nephrectomy.
* Prior palliative radiotherapy in metastatic lesion(s) is permitted, provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated.
* All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to registration. Patients must have recovered from surgery and/or radiotherapy toxicity prior to registration.
* At the time of enrollment, patients must have evidence of metastatic or unresectable disease.
* Paraffin RCC tissue blocks or unstained slides must be obtained for future chemistry staining or every effort made to obtain samples.
* Karnofsky performance status \> 70%.
* Echocardiogram ejection fraction of ≥ 45%
* Age \>18.
* Must meet required initial laboratory values

Exclusion Criteria:

* Patients with true chromophobe, oncocytoma, collecting duct tumor and transitional cell carcinoma are NOT eligible.
* Patients who have received small molecule epithelial growth factor inhibitors (such as Irresa, Tarceva) are excluded.
* Patients who have had prior exposure to sunitinib are excluded.
* No ongoing hemoptysis, or cerebrovascular accident within 12 months, or peripheral vascular disease with claudication on less than 1 block, or history of clinically significant bleeding, because of the potential bleeding and/or clotting risk with this combination therapy.
* No deep venous thrombosis or pulmonary embolus within 12 months of randomization and no ongoing need for full-dose oral or parenteral anticoagulation. Low dose coumadin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin is allowed.
* No evidence of current central nervous system (CNS) metastases. Any imaging abnormality indicative of CNS metastases will exclude the patient from the study.
* No significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, II or IV) angina pectoris requiring nitrate therapy, or recent myocardial infarction (within the last 6 months).
* No active ischemia on electrocardiogram.
* No patients with uncontrolled hypertension (defined as blood pressure of \> 160 mmHg systolic and/or \> 90 mmHg diastolic on medication).
* \- Any ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency) is not permitted. Topical and/or inhaled steroids are allowed.
* Patients with a pre-existing thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication are ineligible.
* No uncontrolled psychiatric disorder.
* Patients with delayed healing of wounds, ulcers, and/or bone fractures are not eligible.
* Patients with a 'currently active' second malignancy other than non-melanoma skin cancers are not eligible.
* Pregnant women are excluded (negative urine or serum pregnancy test required) because of the potential for teratogenic or abortifacient effects of therapy.