Phase II Study of Alternating Sunitinib and Temsirolimus

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

Patients with measurable metastatic renal cell carcinoma (any histology) are eligible. All
patients will be treated as outlined below with sunitinib alternating with temsirolimus.

Patients will be treated continuously, until evidence of progression of disease, or for up to
two cycles following disappearance of all disease.

A cycle is defined as:

Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest Temsirolimus 25mg IV
weekly for 4 weeks followed by a two week rest

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:

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).