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
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Yale University
- Enrollment
- 190
- Locations
- 17
- Primary Endpoint
- Failure-free survival (FFS)
Overview
Brief Summary
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
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, 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: 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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
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
Arms & Interventions
Arm I (ADT, docetaxel)
Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Intervention: Antiandrogen Therapy (Drug)
Arm I (ADT, docetaxel)
Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Intervention: Docetaxel (Drug)
Arm I (ADT, docetaxel)
Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Intervention: Laboratory Biomarker Analysis (Other)
Arm I (ADT, docetaxel)
Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Intervention: Quality-of-Life Assessment (Procedure)
Arm I (ADT, docetaxel)
Participants receive antiandrogen therapy with or without docetaxel at the discretion of the treating physician.
Intervention: Questionnaire Administration (Other)
Arm II (ADT, radical prostatectomy, docetaxel)
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.
Intervention: Antiandrogen Therapy (Drug)
Arm II (ADT, radical prostatectomy, docetaxel)
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.
Intervention: Docetaxel (Drug)
Arm II (ADT, radical prostatectomy, docetaxel)
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.
Intervention: Laboratory Biomarker Analysis (Other)
Arm II (ADT, radical prostatectomy, docetaxel)
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.
Intervention: Quality-of-Life Assessment (Procedure)
Arm II (ADT, radical prostatectomy, docetaxel)
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.
Intervention: Questionnaire Administration (Other)
Arm II (ADT, radical prostatectomy, docetaxel)
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.
Intervention: Radical Prostatectomy (Procedure)
Outcomes
Primary Outcomes
Failure-free survival (FFS)
Time Frame: At 2 years
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.
Secondary Outcomes
- Time to biochemical progression(Up to 2 years)
- Cancer-specific survival(Up to 2 years)
- Overall complication rate(Up to 2 years)
- Overall survival(Through study completion, a minimum of 4 years)