Phase II Study of Alternating Sunitinib and Temsirolimus

Inclusion Criteria

• Histologically confirmed metastatic renal cell cancer with evaluable disease.
• Patients must be at least 2 weeks from their last immunotherapy, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.
• Karnofsky Performance Status ≥60%
• Life expectancy ≥ twelve weeks
• Adequate end organ function:

Cardiac Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal (LLN) as assessed by echocardiography (ECHO) . The same modality used at baseline must be applied for subsequent evaluations.

• Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study and practicing acceptable forms of birth control
• Appropriate Contraception in both sexes
• The patient must be competent and signed informed consent.

EXCLUSION CRITERIA

• Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS.
• In patients with a prior history of invasive malignancy, less than five years in complete remission.
• Have evidence of significant co-morbid illness such as uncontrolled diabetes, hypertension or active infection that would preclude treatment on this regimen.
• Prior treatment with either sunitinib or temsirolimus
• Clinically significant gastrointestinal abnormalities
• Presence of uncontrolled infection.
• Prolongation of corrected QT interval (QTc) > 480 milliseconds - History of any one or more of the following cardiovascular conditions within the past 12 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Coronary artery by-pass graft surgery
• Symptomatic peripheral vascular disease
• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) within the past 12 months.
• History of pulmonary embolism or untreated deep venous thrombosis (DVT)within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible.
• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of

≥150 or diastolic blood pressure (DBP) of ≥ 90. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.

• Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
• Evidence of active bleeding or bleeding diathesis
• Hemoptysis within 6 weeks of first dose of study drug.
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
• Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.
• Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug any minor surgeries (i.e. skin biopsy, tooth extraction, etc.) and recovered from all ill effects.
• Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to sunitinib or temsirolimus.
• Untreated brain metastasis. (Brain metastases that are stable based on radiographic evidence 4 weeks after radiation and/or surgery are permitted).