Single Agent Temsirolimus (Torisel®) in Chemotherapy-naïve Castration-Resistant Prostate Cancer Patients

This is an open label phase II study conducted in patients who have androgen-independent and
castration-resistant prostate cancer but who have not received systemic chemotherapy.
Investigational therapy such as vaccines, immunotherapy, and some oral targeted agents are
NOT considered chemotherapy. Prior use of steroids is not an exclusion criterion.

Patients who meet the inclusion criteria will be allowed to participate. Enrolled patients
will receive single agent Torisel® at 25 mg weekly. Every 4 weeks of therapy will
constitute one cycle of treatment. Patients will continue on therapy until voluntary
withdrawal, toxicity, progression, or the investigator's discretion. Patients will be
followed for 3 years after discontinuation of Torisel®.

Patients are allowed to receive intravenous or oral bisphosphonates for their bone
metastases and are advised to continue androgen blockade while on study.

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.

2. Age 18 years at the time of signing the informed consent form.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Documented prostate cancer regardless of the Gleason score

5. Patients should be considered hormone refractory and castration-resistant. They must
fail LHRH analogues, and anti-androgen withdrawal trial. Failure is confirmed by an
increase in PSA value of 10% or more than the value immediately before.

6. Patients must have measurable disease either biochemically (using PSA) and/or using
the RECIST criteria for visceral organ involvement and/or bone disease. If there is
no disease to follow on scans a PSA value of at least 5 ng per milliliter needs to be
present at baseline to be evaluated for PSA response.

7. ECOG Performance Status of 2 or less.

8. Adequate liver function tests with ALT/AST being < 3x normal, total bilirubin of 1.5
or less, and adequate renal function measured by a creatinine of 2.0 mg/dl or less.
Alkaline phosphatase values are never exclusion criteria if it is deemed related to
bone metastases.

9. Patients need to have adequate bone marrow function.

- ANC of 1000 or above,

- Hgb of 9.0 g/dl or above,

- Platelets of 100,000 or above. If other causes are affecting plts counts such
as autoimmune disorders, patients are allowed on study. Patients with
inadequate bone marrow function that is deemed related to bone marrow
involvement with prostate cancer (cytopenias are due to extensive marrow
infiltration with prostate cancer) are allowed at the investigator's discretion.

10. Patients with other malignancies are allowed as long as there is no evidence of the
other malignancy present at entry time, and it has been 3 years or more since the
treatment for the other disorder was completed. Patients with non-melanoma skin
cancers are allowed to participate in the study.

11. Investigational therapy such as vaccines, immunotherapy, and oral targeted agents are
allowed on this study as long as their last exposure was 4 weeks prior to study
entry. These agents are not considered an exclusion criteria as they are not
considered standard chemotherapy.

12. Patients with known bone metastases are allowed to receive intravenous
bisphosphonates such as aredia or zometa. Patients on oral bisphosphonates are also
allowed.

13. All study participants are encouraged to continue androgen deprivation with an LHRH
analogue.

14. Patients must agree to use a latex condom during sexual contact with a female of
childbearing potential, even if they have had a successful vasectomy and despite the
fact that they are on androgen deprivation.

15. Last treatment for prostate cancer should be at least 4 weeks ago

Exclusion Criteria:

1. Prior systemic chemotherapy for CRPC

2. Prior exposure to TEM

3. Known HIV positive status or infectious hepatitis, type A, B, or C.

4. Known brain metastases.

5. Steroids are allowed concomitantly ONLY IF they are taken for another chronic medical
condition (Such as COPD, Multiple sclerosis…etc)

6. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing and understanding the informed consent form.

7. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he were to participate in the study or confounds the
ability to interpret data from the study.

8. Use of any other experimental drug or therapy within 28 days of baseline.