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

SIMCAP (Surgery in Metastatic Carcinoma of Prostate): Phase 2.5 Multi-Institution Randomized Prospective Clinical Trial Evaluating the Impact of Cytoreductive Radical Prostatectomy Combined With Best Systemic Therapy on Oncologic and Quality of Life Outcomes in Men With Newly Diagnosed Metastatic Prostate Cancer

This is a phase 2.5 international, multi-institution, randomized clinical trial to evaluate the potential therapeutic effect of CRP combined with the BST in men with mPCa prospectively. Such hybrid design permits the inclusion of the patients who have accrued to the phase 2 investigation to phase 3 trial, thereby decreasing the number of patients needed overall (5-7). In the initial phase 2 study, we plan to accrue 190 patients.

PRIMARY OBJECTIVES:

I. To assess the clinical benefit of combining radical surgery - cytoreductive radical prostatectomy (CRP) - with the best systemic therapy (BST) - to be determined by the treating physician in men with newly diagnosed clinical mPCa.

SECONDARY OBJECTIVES:

I. To determine the impact of CRP+BST on time to biochemical progression, cancer-specific survival, overall 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 (Control Group): BST - to be determined by the treating physician (ADT +/- docetaxel at the discretion of the treating physician).

ARM II: CRP + BST

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), M1b (bone metastasis), or M1c (solid organ 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 (i.e prostate radiation, cryotherapy, etc.)
• Give informed consent
• Prostate deemed resectable by surgeon
• Plans to start or has already started ADT no longer than 6 months prior to consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Hemoglobin (HgB) >= 9 g/dL compatible for surgery
• Platelets > 80,000/mcL compatible for surgery
• Aspartate aminotransferase (AST) =< 2x upper limit of normal (ULN) compatible for surgery
• 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 consent
• Life expectancy of less than 6 months prior to consent
• Active spinal cord compression
• Deep vein thrombosis (DVT) / pulmonary embolism (PE) in the past 6 months prior to consent
• Previous local therapy for prostate cancer
• Patients who have chemotherapy or radiotherapy for non-prostate cancer related treatment within 3 weeks prior to consent