A Safety and Efficacy Study of SHR3680 in Metastatic Castration-Resistant Prostate Cancer Patients
Study Details
Study Description
Brief Summary
This study evaluates the tolerability, safety, pharmacokinetics and efficacy of SHR3680 in patients with metastatic castration-resistant prostate cancer (mCPRC). All participants will receive SHR3680.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Androgenic signaling plays a pivotal role in the development of prostate cancer. Androgen deprivation therapy is the mainstay treatment for this cancer in the metastatic setting, but the disease eventually develops to castration-resistant prostate cancer (CRPC) mainly due to the overexpression of androgen receptors (AR) and continued AR activation.
SHR3680 is a novel strong AR antagonist. By competitively binding to AR, SHR3680 inhibits androgen-mediated translocation of AR to the nucleus, binding of AR to Deoxyribonucleic acid (DNA), and finally the transcription of AR target genes, thus possibly resulting in a specific and strong anti-tumor effect on prostate cancer. Unlike first-generation AR antagonists (e.g. bicalutamide), which undergoes an antagonist-to-agonist switch to stimulate AR in the setting of AR overexpression in CRPC, SHR3680 is a full antagonist of AR and thus it is supposed to be more effective for the treatment of CRPC.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SHR3680 Tablet |
Drug: SHR3680
SHR3680 is administrated orally, qd, 28 days as one cycle. Patients may continue SHR3680 until disease progression or unacceptable toxicity.
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) [12 weeks]
For Phase 1 portion of study; maximum-tolerated dose (MTD) will be defined as the maximum dose level at which no more than one out of three subjects experience a dose-limiting toxicity (DLT) within the first 12 weeks of multiple dosing
- Radiological progression-free survival [24 months]
For Phase 2 portion of study
Secondary Outcome Measures
- Number of participants with treatment-related adverse events [24 months]
Adverse events are assessed by CTCAE v4.0
- The percentage of patients reaching at least a 50% reduction in prostate specific antigen (PSA) as compared to baseline at 12 weeks [12 weeks]
- Time to prostate specific antigen (PSA) progression [24 months]
Prostate specific antigen (PSA) progression is defined by the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.
- Objective response rate [24 months]
- Quality of life [24 months]
Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)
- Peak plasma concentration (Cmax) [12 weeks]
- Area under the plasma concentration versus time curve (AUC） [12 weeks]
- T1/2 (Half-life) [12 weeks]
The time required for the plasma concentration of a drug to be reduced by 50%
Eligibility Criteria
Criteria
Inclusion Criteria:
-
ECOG performance scale 0 - 1.
-
Life expectancy of more than 6 months.
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Histologically or cytologic confirmed prostate adenocarcinoma without neuroendocrine differentiation or small cell features
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Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy
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Evidence of prostate cancer progression by radiographic or PSA criteria
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Radiological evidence of distant metastatic lesions
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Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the screening visit
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Adequate hepatic, renal, heart, and hematologic functions (platelets > 80 × 10e9/L, neutrophil > 1.5 × 10e9/L, Hb >90 g/L,total bilirubin and creatinine within upper limit of normal(ULN), and serum transaminase≤1.5×the ULN).
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Signed and dated informed consent.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.
Exclusion Criteria:
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Treatment with androgen receptor antagonists, 5-alpha reductase inhibitors, estrogens, or chemotherapy within 4 weeks of enrollment or plans to initiate treatment with any of these drugs during the study
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Prior treatment with enzalutamide, abiraterone, or ketoconazole for prostate cancer
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History of seizure or any conditions that may predispose to seizure
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Concurrent or planned treatment with corticosteroids, medications known to have seizure potential, or herbal products known to decrease PSA levels
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Planned to initiate any other anti-tumor therapies during the study
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Less than 4 weeks from the last clinical trial
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Evidence of brain metastasis or primary tumors
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Clinically significant cardiovascular diseases
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Abuse of alcohol or drugs
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Severe concurrent disease, infection, or bone metastasis that, in the judgment of the investigator, would make the patient inappropriate for enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Hosptial | Beijing | Beijing | China | |
| 2 | Chinese PLA General Hospital | Beijing | Beijing | China | |
| 3 | Chongqing Cancer Hospital | Chongqing | Chongqing | China | |
| 4 | Henan Cancer Hospital | Zhenzhou | Henan | China | |
| 5 | Hunan Cancer Hospital | Changsha | Hunan | China | |
| 6 | Jiangsu Cancer Hospital | Nanjing | Jiangsu | China | |
| 7 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China | 200032 |
| 8 | Huadong Hospital Affiliated to Fudan University | Shanghai | Shanghai | China | |
| 9 | The Second Affiliated Hospital of Xi'an Jiaotong University | Xi'an | Shanxi | China | |
| 10 | Tianjin Medical University Cancer Institute & Hospital | Tianjin | Tianjin | China | |
| 11 | The Second Affiliated Hospital of Zhejiang University School of Medicine | Hangzhou | Zhejiang | China | |
| 12 | Zhejiang Cancer Hospital | Hangzhou | Zhejiang | China |
Sponsors and Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
Investigators
- Principal Investigator: Dingwei Ye, M.D., Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHR3680-001