Phase I/II Trial of RAD001 Plus Nexavar in Patients With Kidney Cancer

Inclusion Criteria:

• Histologic confirmed predominant clear cell renal cell carcinoma.
• Patients must have progressive metastatic disease.
• Paraffin RCC tissue blocks or unstained slides must be available.
• Karnofsky performance status > 70% .
• Not pregnant
• Age > 18
• Initial laboratory values must meet requirements
• Phase I: No more than three prior systemic and/or investigative therapy for MRCC. Previous therapy may include prior single agent exposure to RAD001 or Nexavar®. Four weeks must have elapsed from previous therapy.
• Phase II: No more than one prior systemic and/or investigative therapy of any kind for MRCC. Four weeks must have elapsed from previous therapy.
• Phase II: Previous therapy may not include RAD001 or Nexavar®.
• Phase II: Patients with primary tumor in place are strongly encouraged to undergo nephrectomy prior to initiation of study agent.
• Phase II: Prior palliative radiotherapy to metastatic lesion(s) is permitted. Patient must have adequately recovered from the acute toxicities of this treatment.
• Phase II: All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to registration.

Exclusion Criteria:

• 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.
• No deep venous thrombosis or pulmonary embolus within one year and no ongoing need for full-dose oral or parenteral anticoagulation.
• No evidence of current central nervous system (CNS) metastases.
• No significant cardiovascular disease
• No patients with uncontrolled hypertension
• Any ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency) or other immunosuppressants are not permitted.
• 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. Patients are not considered to have a 'currently active' malignancy if they have completed anti-cancer therapy and are considered by their physician to be a less than 30% risk of relapse.
• Pregnant women are excluded
• All fertile patients must use adequate contraception (barrier method) while on study and for three months thereafter. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
• Prior treatment with any investigational drug within the preceding 4 weeks.
• Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, severe infection, severe malnutrition, ventricular arrhythmias, chronic liver or renal disease, active upper GI tract ulceration).
• A known history of HIV seropositivity.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).