Phase II Trial of Bevacizumab(Avastin) and RAD001(Everolimus)in the Treatment of Patients With Advanced Clear Cell Renal Carcinoma

Inclusion Criteria:

- Histologically documented metastatic or unresectable locally recurrent clear cell
renal carcinoma.

- In patients with mixed histologies, the clear cell component must comprise ≥ 75% of
the cancer

- Previous nephrectomy is required with the following exceptions:

- Primary tumor < 5cm

- Extensive liver ( > 30% of liver parenchyma)or

- Multiple (> 5) bone metastases, making nephrectomy a clinically contraindicated
procedure

- Patients may have had a maximum of 1 previous systemic regimen for metastatic disease

- Patients may not have received previous bevacizumab. However, patients who have
received other agents with anti-angiogenic activity (eg. sorafenib, SU11248,
AG-013736, PTK787, thalidomide) as part of first-line treatment are eligible

- Patients may not have received previous treatment with m-TOR inhibitors.

- ECOG performance status 0 or 1

- Measurable disease

- Adequate liver, kidney and bone marrow function

- No previous systemic treatment or radiation therapy for at least 2 weeks prior to
study entry

- Patients must be able to understand the nature of this study and give written
informed consent

Exclusion Criteria:

- Age < 18 years

- Treatment with > 1 previous systemic regimen for metastatic renal carcinoma

- History of acute myocardial infarction within 6 months

- Clinically significant cardiovascular disease

- History of stroke within 6 months

- Patients with active brain metastases

- Patients with meningeal metastases

- Women who are pregnant or lactating

- Patients who have been treated within 5 years for other invasive cancers

- Patients with history or evidence by physical examination of CNS disease

- Patients with clinical history of hemoptysis or hematemesis

- Patients with history of deep vein thrombosis or thromboembolic disease requiring
full dose anticoagulation

- Patients with major surgical procedures, open biopsies, or significant traumatic
injuries within 28 days or anticipated need for major surgical procedure during the
course of the study

- Patients with peg-tubes or G-tubes

- Patients are ineligible if a fine needle aspiration biopsy has been performed within
seven days

- Patients with proteinuria

- Patients with any non-healing wound, ulcer, or long-bone fracture

- Patients with any history of a bleeding diathesis or coagulopathy

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months

- Patients who have received any other experimental drug within 28 days of starting
treatment

- History of any other severe and/or uncontrolled medical disease

- History of HIV infection

- Chronic treatment with steroids or other immunosuppressive agents

- Patients with impaired GI function that compromises the ability to swallow or absorb
RAD001

- Patients who are unwilling or unable to comply with the protocol