Stage IV Prostate Adenocarcinoma AJCC v7
Conditions
Brief summary
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.
Detailed description
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
Interventions
DRUGAntiandrogen Therapy
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.
DRUGDocetaxel
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.
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDUREQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
PROCEDURERadical Prostatectomy
Undergo cytoreductive radical prostatectomy
Sponsors
Yale University
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure-free survival (FFS) | At 2 years | Failure is defined as any one of the following events: PSA progression, clinical progression, radiographic progression, or death. 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
| Measure | 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 |
Countries
Australia, China, Japan, South Korea, Taiwan, United States
Contacts
PRINCIPAL_INVESTIGATORIsaac Kim, MD
Yale University
Outcome results
None listed