Alternating Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma: A Phase II Study of Alternating Sunitinib and Temsirolimus

Inclusion Criteria

Inclusion Criteria

- Histologically confirmed metastatic renal cell cancer with evaluable disease.

- Patients must be at least 4 weeks from their last immunotherapy, radiation, 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 or multigated acquisition (MUGA) scan. 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.

- Use of corticosteroids or other immunosuppression (if patient had been taking
steroids, at least 4 weeks must have passed since the last dose).

- 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:

1. Cardiac angioplasty or stenting

2. Myocardial infarction

3. Unstable angina

4. Coronary artery by-pass graft surgery

5. Symptomatic peripheral vascular disease

6. 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).