Therapeutic Effect of Cytoreductive Radical Prostatectomy in Men With Newly Diagnosed Metastatic Prostate Cancer

PRIMARY OBJECTIVES:

I. To assess the clinical benefit of combining radical surgery ? cytoreductive radical
prostatectomy (CRP) - with the best systemic therapy (BST) in men with newly diagnosed
clinical M1a or M1b metastatic prostate cancer (mPCa).

SECONDARY OBJECTIVES:

I. To determine the impact of CRP+BST on time to biochemical progression, cancer-specific
survival, complication rates, and quality of life (QOL) in patients with mPCa.

II. To determine the transcription levels of bone morphogenetic protein -6 (BMP-6) and
transforming growth factor-beta (TGF-?).

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive antiandrogen therapy with or without docetaxel at the discretion
of the treating physician.

ARM II: Participants receive antiandrogen therapy for at least 1 month, then undergo
cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may
receive docetaxel within 3 months after surgery at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 6 months from time of
progression.

Inclusion Criteria:

- Histologically proven adenocarcinoma of the prostate

- Evidence of metastasis by magnetic resonance imaging (MRI)/computed tomography (CT)
scan, bone scan, or histologic confirmation

- Clinical stage M1a (distant lymph node positive), or M1b (bone metastasis)

- If solitary lesion, metastasis confirmed with either biopsy or two independent imaging
modalities (i.e. CT and PET [positron emission tomography], bone scan and MRI,
modality at the discretion of the treating physician)

- No previous local therapy for prostate cancer

- Give informed consent

- Prostate deemed resectable by surgeon

- Started antiandrogen therapy (ADT) no longer than 6 months prior to randomization

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Hemoglobin (HgB) >= 9 g/dL compatible for surgery

- Platelets > 80,000 compatible for surgery

- Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =< 2x upper limit of
normal (ULN) compatible for surgery

Exclusion Criteria:

- Refuses to give informed consent

- Deemed to have unresectable disease by surgeon

- Received ADT for more than 6 months prior to randomization

- Life expectancy of less than 6 months prior to randomization

- Known spinal cord compression

- M1c disease (solid organ metastasis)

- Deep vein thrombosis (DVT) / pulmonary embolism (PE) in the past 6 months prior to
randomization

- Previous local therapy for prostate cancer

- Previous chemotherapy for prostate cancer

- Patients who have chemotherapy, radiotherapy or oral antifungal agents (ketoconazole,
itraconazole, fluconazole) within 3 weeks prior to entering the study or those who
have not recovered (e.g. back to baseline or grade 1) from adverse events due to
agents administered more than 3 weeks earlier

- Any drug interactions that are deemed to be medically significant would require a
washout of 5-half-lives of the interaction agent before enrollment can occur