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

Study Overview
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Brief Summary
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This randomized phase II trial studies how well surgical removal of the prostate and antiandrogen therapy with or without docetaxel work in treating men with newly diagnosed prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Antiandrogen therapy may lessen the amount of androgens made by the body. Drugs used in chemotherapy, such as docetaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Surgery, antiandrogen therapy and docetaxel may work better in treating participants with prostate cancer.

Detailed Description
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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 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 prior to surgery at the discretion of the treating physician. After completion of study treatment, patients are followed up every 6 months from time of progression.

Official Title
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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

Conditions
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Stage IV Prostate Adenocarcinoma AJCC v7

Intervention / Treatment
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* Drug: Antiandrogen Therapy
* Drug: Docetaxel
* Other: Laboratory Biomarker Analysis
* Procedure: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Procedure: Radical Prostatectomy


Participation Criteria
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Eligibility Criteria
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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 antiandrogen therapy (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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (ADT, docetaxel)<br>Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician. | Drug: Antiandrogen Therapy<br>* To demonstrate at least 30% improvement in FFS at 2 years after randomization with the power of 90% and error of 5% on a one-sided exponential MLE test.<br>* Other names: Hormone-Deprivation Therapy;Drug: Docetaxel<br>* To demonstrate at least 30% improvement in FFS at 2 years after randomization with the power of 90% and error of 5% on a one-sided exponential MLE test.<br>* Other names: Taxotere Injection Concentrate;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (ADT, radical prostatectomy, docetaxel)<br>Participants receive antiandrogen therapy for at least 1 month, then undergo cytoreductive radical prostatectomy. Participants continue antiandrogen therapy and may receive docetaxel prior to surgery at the discretion of the treating physician. | Drug: Antiandrogen Therapy<br>* To demonstrate at least 30% improvement in FFS at 2 years after randomization with the power of 90% and error of 5% on a one-sided exponential MLE test.<br>* Other names: Hormone-Deprivation Therapy;Drug: Docetaxel<br>* To demonstrate at least 30% improvement in FFS at 2 years after randomization with the power of 90% and error of 5% on a one-sided exponential MLE test.<br>* Other names: Taxotere Injection Concentrate;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Radical Prostatectomy<br>* Undergo cytoreductive radical prostatectomy<br>* Other names: Prostatovesiculectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival (FFS) | Failure is defined as any one of the following events: PSA progression, clinical progression, radiographic progression, or death from prostate cancer. The % of men who fail within 2 years of randomization will be compare between the two groups using a one-sided log-rank test. | At 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer-specific survival |  | Up to 2 years | 
| Overall complication rate |  | Up to 2 years | 
| Time to biochemical progression |  | Up to 2 years | 
| Overall survival |  | Through study completion, a minimum of 4 years |