Bevacizumab (Avastin) and RAD001(Everolimus)in the Treatment of Advanced Clear Cell Renal Carcinoma

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

This phase II trial will evaluate the combination of bevacizumab + RAD001 in patients with metastatic renal cell carcinoma. In this trial the investigators will evaluate this combination in patients previously untreated with any anti-angiogenesis agent and patients who have previously received one prior regimen containing an anti-angiogenesis agent.

All eligible patients will receive:

• Bevacizumab 10mg/kg, IV infusion, every 2 weeks
• RAD001 10 mg by mouth daily

All patients will be evaluated for response after completing two courses (8 weeks) of treatment. Patients with objective tumor response or stable disease will continue treatment with bevacizumab adn RAD001 on the same schedule. Treatment will continue until disease progression occurs.

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