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This is an open-label study that includes three substudies of random distribution. First, a sample of the primary tumor will be obtained and will be analyzed by an immunohistochemical technique to determine several markers. Depending on the expression of these markers, the patients will be characterize as group 1 (Luminal phenotype), group 2 (Neuroendocrine phenotype) or group 3 (Atypical phenotype) and a random assignment will be performed to standard or experimental treatment.
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogenous disease with at least 3 intrinsic subtypes including luminal, neuroendocrine, and atypical phenotypes. Different subtypes have different prognosis and treatment sensitivity. Thus, it would be more suitable to administer different therapy in different subtypes. Therefore, the investigators designed this phase 2 randomized clinical trial to explore potential effective regimens in variable subtypes of mCRPC. Patients were first classified into Luminal type, Neuroendocrine type and Atypical type by immunohistochemistry exam of FKBP5/AR-WT/AR-v7/CgA/SYN/YAP1 in core needle biopsy and then randomized to received either standard or experimental treatment.
Group 1 (Luminal type):
Standard treatment: Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Experimental treatment: Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+Prednisone (5 mg, twice daily)
Group 2 (Neuroendocrine type):
Standard treatment: Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Experimental treatment: Goserelin (3.75mg, once every 4 weeks)+Carboplatin (area under the curve 5 on day 1 every 3 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Group 3 (Atypical type):
Standard treatment: Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily)
Experimental treatment: Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+targeted therapy according to next Generation Sequencing (NGS)+Prednisone (5 mg, twice daily); or Goserelin (3.75mg, once every 4 weeks)+Abiraterone alone+Prednisone (5 mg, twice daily) if no druggable gene mutation detected. The detailed Individual treatment see below.
The duration of chemotherapy is 6-10 cycles. Primary endpoint is the overall survival (OS) in each subtypes. Secondary endpoints include progression free survival (PFS), PSA response rate and safety. Tissue samples and blood samples will be collected at baseline and during treatment. There will be exploratory biomarkers analyses to identify predictive markers for efficacy in every subtypes.
Targeted Therapy: Participants with druggable gene mutations will receive the corresponding molecular targeted drugs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Luminal type-1 | Active Comparator | Standard treatment |
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| Luminal type-2 | Experimental | Experimental treatment |
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| Neuroendocrine type-1 | Active Comparator | Standard treatment |
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| Neuroendocrine type-2 | Experimental | Experimental treatment |
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| Atypical type-1 | Active Comparator | Standard treatment |
|
| Atypical type-2 | Experimental | Experimental treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Luminal type-1 | Drug | Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | OS was defined as the duration from the initiation of treatment to death of any cause | Up to 40 months |
| Measure | Description | Time Frame |
|---|---|---|
| PSA-Progression free survival (pPFS) | PSA progression was defined as an increase in the PSA level of 25% or more above the nadir (and by≥2 ng/ml), with confirmation of 4 or more weeks later | Up to 40 months |
| Radiographic progression free survival (rPFS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shimiao Zhu, MD,PhD | Contact | +86 137 5243 6539 | zhushimiao@tijmu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tianjin Medical Unversity Second Hospital | Recruiting | Tianjin | 300211 | China |
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| Luminal type-2 | Drug | Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+Prednisone (5 mg, twice daily) |
|
| Neuroendocrine type-1 | Drug | Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily) |
|
| Neuroendocrine type-2 | Drug | Goserelin (3.75mg, once every 4 weeks)+Carboplatin (area under the curve 5 on day 1 every 3 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily) |
|
| Atypical type-1 | Drug | Goserelin (3.75mg, once every 4 weeks)+Docetaxel (75 mg/m2 on day 1 every 3 weeks)+Prednisone (5 mg, twice daily) |
|
| Atypical type-2 | Drug | Goserelin (3.75mg, once every 4 weeks)+Abiraterone (1000 mg, once daily)+ targeted therapy according to next Generation Sequencing (NGS)+ Prednisone (5 mg, twice daily), or Goserelin (3.75mg, once every 4 weeks)+Abiraterone+ Prednisone (5 mg, twice daily) if no druggable gene mutation detected. |
|
rPFS was defined 1) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria; or 2) as at least two new lesions on first post-treatment bone scan, with at least two additional lesions on the next bone scan |
| Up to 40 months |
| PSA response rate | PSA response is defined as ≥ 50% decline in PSA level from baseline, maintained for≥ 4 weeks | Up to 40 months |