Rituximab Neoadjuvant Therapy in Patients With Prostate Cancer Scheduled to Undergo Radical Prostatectomy

This is an open label, single institution, pilot study of rituximab neoadjuvant therapy in
patients with high risk prostate cancer scheduled to undergo radical prostatectomy. Prior to
prostatectomy, patients will receive one treatment cycle (28 days) of rituximab 375 mg/m2
intravenously once weekly. Patients will be scheduled to undergo radical prostatectomy
within two weeks of completing study treatment. Tissue from prostatectomy will be used for
immunohistochemistry (IHC) staining of pharmacodynamic markers.

Inclusion Criteria:

- Ability to understand and provide written informed consent.

- Patient has EITHER:

- A Kattan nomogram predicted probability of being disease free 5 years after
surgery of < 60%, OR

- A Gleason sum ≥ 8.

- Indicated for radical prostatectomy.

Note: candidates for radical prostatectomy are still eligible even if they have a history
of deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident or
currently requiring systemic anticoagulation.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Appendix A).

- Males aged ≥ 18 years.

- Adequate organ function as defined below measured within 21 days of study entry:

- Hematology:

- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

- Platelet count ≥ 100 x 109/L

- Hemoglobin ≥ 9.0 g/dL

- White blood cell (WBC) count ≥ 3.0 x 109/L

- Biochemistry:

- Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT)
and alanine transaminase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤ 2 x
institution's upper limit of normal (ULN)

- Total bilirubin <1.5 times ULN

- Serum creatinine and blood urea nitrogen (BUN)<1.5 times ULN

- Na, K Cl, carbon dioxide (CO2), Ca, phosphate (PO4) within institutional limits

- Available prostate biopsy specimen which is evaluable for B lymphocyte count.

Exclusion Criteria:

- Received prior treatment for prostatic adenocarcinoma including prior surgery
(excluding TURP), radiation therapy, or chemotherapy.

- Current or past use of investigational agents within 4 weeks of study enrollment.

- Evidence of metastatic disease on cross sectional imaging or bone scan.

- History of hepatitis B or C, hepatitis immunodeficiency virus (HIV), tuberculosis or
a chronic infection of any type.

- Positive test results for chronic hepatitis B infection (defined as positive HBsAg
serology).

- Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology
testing).