A Phase II Trial of Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma
- 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.
- 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
- 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