Trial of eRapa in Prostate Cancer Patients

This is a phase Ib trial of encapsulated rapamycin to determine safety,
pharmacokinetics/pharmacodynamics, and immunologic impact in patients with low risk prostate
cancer under active surveillance. This new formulation, encapsulated rapamycin (sirolimus),
provides a more predictable bioavailability of this drug than [the other formulation]. The
encapsulated and targeted rapamycin (eRapa) can be delivered at a consistent and lower
dosage, not only improving the toxicity profile but also capitalizing on the newly
appreciated mechanism of partial and/or intermittent mTOR inhibition, making eRapa an ideal
immuno-oncologic and chemopreventative agent. Low dose rapamycin has been shown to prevent
cancer formation, progression, and/or recurrence in the majority of cancer histologies
including the most prevalent: lung, breast, prostate, and colon cancers.

Inclusion Criteria:

The patient must:

- Have pathologically (histologically) proven diagnosis of prostate cancer with a
Gleason score ≤7 (3+4) and already undergoing active surveillance

- Be able to give informed consent

- Be age 18 or older

Exclusion Criteria:

- Prostate cancer with a Gleason score >7

- Unable to give informed consent

- Age < 18

- Immunosuppressed state (e.g., HIV, use of chronic steroids)

- Active, uncontrolled infections

- On medications with strong inhibitors or inducers of CYP3A4 and or P-gp.

- On agents known to alter rapamycin metabolism significantly (Appendix H)

- Have another cancer requiring active treatment (except basal cell carcinoma or
squamous cell carcinoma of the skin)

- Individuals with a reported history of liver disease (e.g., cirrhosis)

- Individuals who are not a good candidate for active surveillance in their treating
physician's opinion

- Have a medical condition (e.g., anemia, anticoagulated) for which repeated phlebotomy
may be problematic.

- Uncontrolled hypertension.

- Individuals that have abnormal screening vital organ function prior to enrollment

- Liver Function Test

- Bilirubin >2.0

- Alkaline phosphatase >5x upper limit of normal (ULN)

- ALT/AST >2x ULN

- Complete Blood Count:

- WBC elevated above the normal standard per the testing laboratory

- Hgb/Hct below the normal standards of the testing lab

- Platelets below the normal standards of the testing lab

- Total Cholesterol >240 mg/dL

- Triglycerides > 200 mg/dL

- Serum creatinine >2 and BUN >30

- Urinary protein: proteinuria >1+ on urinalysis or >1 gm/24hr