Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma

Inclusion Criteria:

Histologically confirmed renal cell carcinoma in either primary or metastatic lesions. Non-clear histology will be allowed.
Disease progression on a VEGF-targeted tyrosine kinase inhibitor as the most recent therapy or have experienced intolerable toxicity so as require discontinuation. Only one prior VEGF-targeted tyrosine kinase inhibitor.
Must be off of VEGF-targeted tyrosine kinase inhibitor for 2 weeks or greater.
One measurable lesion which is not curable by standard radiation therapy or surgery.
The enrolling site must agree to obtain paraffin-embedded tumor blocks or at least 10 unstained, paraffin-embedded slides for submission for correlative studies.
18 years of age or older
ECOG Performance Status of 0 or 1
Baseline laboratory values as outlined in the protocol
Life expectancy of greater than 3 months
No prior malignancy diagnosed within the past three years, other than superficial basal cell and superficial squamous cell, or carcinoma in situ of the cervix.

Exclusion Criteria:

Known CNS disease, except for treated brain metastases
Previously treated with avastin or mTOR inhibitors
Other then VEFG-targeted TKI, patients may only have had prior immunotherapy or chemotherapy for stage IV disease
History of allergic reaction to Chinese hamster ovary cell products, other recombinant antibodies, or compounds of similar chemical or biologic composition to avastin or temsirolimus
History of bleeding diathesis or coagulopathy. Therapeutic anticoagulants are allowed
Patients with clinically significant cardiovascular disease
Patients receiving enzyme-inducing antiepileptic drugs or any other CYP3A4 inducer such as rifampin or St. John's wort
No serious non-healing wound, ulcer or bone fracture
No uncontrolled intercurrent illness including , but not limited to, ongoing active infection requiring parental antibiotics or psychiatric illness/social situations that would limit compliance with study requirements
HIV-positive receiving combination anti-retroviral therapy
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
Core biopsy or other minor surgical procedure, excluding placement of vascular access device, within 7 days prior to enrollment on study
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
Known hypersensitivity to any component of avastin or temsirolimus
Life expectancy of less than 12 weeks
History of hemoptysis within 1 month prior to day 1