A Phase II, Multicenter, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Tarceva (Erlotinib Hydrochloride) in Combination With Avastin (Bevacizumab) Versus Avastin Alone for Treatment of Metastatic Renal Cell Carcinoma

Inclusion Criteria:

- Written informed consent

- Histologically confirmed RCC of clear cell histology

- Confirmed metastatic RCC

- Age >=18 years

- ECOG performance status of 0 or 1

- Life expectancy >=3 months

- Prior nephrectomy

- Measurable disease, as defined by RECIST

- Use of an acceptable means of contraception (potentially fertile men and women)

Exclusion Criteria:

- RCC with predominantly sarcomatoid features

- Prior systemic or adjuvant therapy for RCC

- Prior radiotherapy for RCC within 28 days prior to Day 0, with the exception of
single fraction radiotherapy given for the indication of pain control

- Treatment with Avastin, Tarceva, or other agents, either investigational or marketed,
that act by either EGFR inhibition or anti-angiogenesis mechanisms

- 24-hour urine collection with >=1 g of protein

- INR >=1.5, except for subjects receiving warfarin therapy

- Serum creatinine >2.0 mg/dL

- Serum calcium >10 mg/dL (corrected)

- Absolute neutrophil count (ANC) <1500/uL

- Platelet count <75,000/uL

- Total bilirubin >2.0 mg/dL

- AST or ALT >5× the upper limit of normal (ULN) for subjects with documented liver
metastases; >2.5 × ULN for subjects without evidence of liver metastases

- LDH >1.5× ULN

- Hemoglobin <9 gm/dL (may be transfused or receive epoetin alfa [e.g., Epogen] to
maintain or exceed this level)

- History of serious systemic disease, including myocardial infarction within the last
6 months, uncontrolled hypertension (blood pressure >160/110 mmHg on medication),
unstable angina, New York Heart Association (NYHA) Grade II or greater congestive
heart failure, unstable symptomatic arrhythmia requiring medication (subjects with
chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular
tachycardia, are eligible), or Grade II or greater peripheral vascular disease

- History of acute stroke within 6 months prior to randomization

- Patients on dialysis

- Other invasive malignancies, including bladder cancer and low-grade endometrial
cancer, within 5 years of randomization (other than squamous or basal cell carcinoma
of the skin)

- Pregnancy or breast feeding

- Inability to comply with study and/or follow-up procedures

- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the subject at high risk from
treatment complications

- Serious, non-healing wound, ulcer, or bone fracture

- Evidence of bleeding diathesis or coagulopathy

- History or clinical evidence of central nervous system or brain metastases

- History of bowel or gastric perforation

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the
course of the study

- Fine needle aspirations or core biopsies within 7 days prior to Day 0