A Phase II Trial of 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