Bevacizumab (Avastin) and RAD001(Everolimus)in the Treatment of Advanced Clear Cell Renal Carcinoma
Condition: Kidney Cancer
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell
Intervention: bevacizumab; RAD001
Intervention description: Bevacizumab 10mg/kg, IV infusion, every 2 weeks; RAD001 10 mg by mouth daily
Intervention MeSH terms: Bevacizumab; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: kidney cancer; bevacizumab

Summary:

      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.
    

Eligibility criteria:

        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