Sunitinib Plus Temsirolimus in Patients With Renal Cell Cancer (RCC)

The Study Drugs:

Sunitinib is designed to block pathways that control important events (such as the growth of
blood vessels) that are essential for the growth of cancer.

Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells
to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of the combination of sunitinib and temsirolimus based on when you joined this study.
There will be 2 stages in this study.

Up to 5 dose levels of the study drug combination will be tested in Stage 1. Two (2)
participants will be enrolled at each dose level. The first group of participants will
receive the lowest dose level. Each new group will receive a higher dose than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of the study drug combination is found.

During Stage 2, different doses of the individual study drugs will be tested based on the
highest tolerable combination dose that was found in Stage 1.

Study Drug Administration:

During each 3-week "study cycle," you will take sunitinib 1 time each day (either with or
without food) for 2 weeks followed by 1 week of rest with no study drug.

You will receive temsirolimus by vein 1 time every week over 30-60 minutes. About 30 minutes
before you receive temsirolimus, you will receive Benadryl (diphenhydramine) by vein over 30
minutes to help prevent side effects.

If you have any side effects from any of the drugs, tell the study doctor right away. The
study doctor may then lower the dose or keep the dose level the same.

Study Visits:

Every week (right before you receive temsirolimus), blood (about 2 teaspoons) will be drawn
for routine tests.

On Day 1 of every cycle:

- You will have a physical exam, including measurement of your vital signs.

- You will be asked about any drugs or treatments you may be receiving.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests (in addition to the weekly
blood draw described above).

Every 6 weeks,:

- You will have the same imaging scans (CT and/or MRI scan) that you had at the screening
visit. If you have stable disease after 2 scans, you will have these every 12 weeks.

- Blood (about 2 teaspoons) will be drawn to check your thyroid function.

- Urine will be collected for routine tests.

Blood Pressure Monitoring:

During the first 3 weeks of the study, your blood pressure will be checked weekly. This may
be done at your local doctor's office. You should write down your blood pressure each time
it is checked in a blood pressure journal that the study staff will give you and bring it
with you when you see your doctor.

Length of Study:

You will remain on study for as long as you are benefiting. You will be taken off study if
the disease gets worse or if you have intolerable side effects.

End-of-Study Visit:

After the last dose of study drug, you will have an end-of-study visit. At the end-of-study
visit, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your vital signs.

- You will be asked about any drugs or treatments you may be receiving.

- You will be asked about any side effects you may have experienced since your last
visit.

This is an investigational study. Sunitinib and temsirolimus are both FDA approved and
commercially available for the treatment of advanced kidney cancer. The use of the drugs in
combination is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with confirmed metastatic RCC of any histological subtype

2. Patients must have evaluable disease

3. Age >/= 18 years. Because no dosing or adverse event data are currently available on
the use of these targeted agents in patients < 18 years of age, children will be
excluded from this study. RCC in patients < 18 is exceedingly rare in any event.

4. Eastern Cooperative Oncology Group (ECOG) performance status
5. Patients must have adequate organ and marrow function within 14 days as defined
below: a) Absolute neutrophil count >/= 1,500/µL; b) Platelet count >/= 100,000/µL;
c) Hemoglobin >/= 9.0 g/dL (may be transfused to maintain or exceed this level); d)
Total bilirubin 2.5 g/dL; f) Serum creatinine mg/dl; g) AST (SGOT) and ALT (SGPT) normal for subjects without evidence of liver metastases; h) AST (SGOT) and ALT
(SGPT) documented liver metastases

6. Female patients of childbearing potential must have a normal serum beta human
chorionic gonadotropin (beta-hCG) within 24 hours prior to beginning treatment on the
study due to the possible teratogenic effect.

7. Patients of child fathering or childbearing potential must agree to practice a form
of medically acceptable birth control while on study

8. Patients must give written informed consent prior to initiation of study-related
procedures. Patients with a history of major psychiatric illness must be judged able
to fully understand the investigational nature of the study and the risks associated
with the therapy

9. Patients must be able to swallow pills

10. Both men and women and members of all races and ethnic groups are eligible for this
trial

Exclusion Criteria:

1. No prior malignancy is allowed, except for non-melanoma skin cancer, in situ
carcinoma of any site, or other cancers for which the patient has been definitively
treated and disease free for 2 years. Patients with controlled brain metastases are
eligible.

2. Patients must not be scheduled to receive another anticancer drug while on this
study. Patients are permitted to be on concomitant bisphosphonates or megestrol
acetate

3. Patients must not have had a stroke or TIA within 6 months

4. Patients must not have uncontrolled infections that could be worsened by anticancer
therapy or interfere with this study

5. Patients must not have clinically significant cardiovascular disease, defined as
myocardial infarction (or unstable angina) within 6 months, New York Heart
Association (NYHA) Grade II or greater congestive heart failure, serious cardiac
dysrhythmia refractory to medical management, or peripheral vascular disease (Grade
III or greater)

6. Patients must not have uncontrolled hypertension, defined as > 140/90 in either
systolic or diastolic component (treatment of hypertension with medications is
permitted)

7. Symptomatic peripheral vascular disease

8. Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with these agents,
breast-feeding should be discontinued if the mother is enrolled on this trial

9. Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy. In addition, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with some of these agents

10. Patients must not have a clinical history of coagulopathy or bleeding diathesis

11. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450
enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital) or
CYP3A4 inhibitors is not recommended on this study.

12. Patients with significant baseline proteinuria defined as > grade 2 by screening U/A
will be excluded if they have > 2 g protein by urine protein over creatinine (UPC)
ratio

13. 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

14. Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device within 7 days prior to study enrollment

15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment

16. Non-healing wound, ulcer, or bone fracture

17. Known hypersensitivity to any component of sunitinib malate, or temsirolimus