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A Safety and Efficacy Study of SHR3680 in Metastatic Castration-Resistant Prostate Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02691975
Recruitment Status : Recruiting
First Posted : February 25, 2016
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

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
Hormone Refractory Prostate Cancer Metastatic Prostate Carcinoma Drug: SHR3680 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label, Dose-Escalation and -Expansion, Safety, Pharmacokinetics and Efficacy Study of SHR3680 in Patients With Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date : April 12, 2016
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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.




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 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

  2. Radiological progression-free survival [ Time Frame: 24 months ]
    For Phase 2 portion of study


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events [ Time Frame: 24 months ]
    Adverse events are assessed by CTCAE v4.0

  2. The percentage of patients reaching at least a 50% reduction in prostate specific antigen (PSA) as compared to baseline at 12 weeks [ Time Frame: 12 weeks ]
  3. Time to prostate specific antigen (PSA) progression [ Time Frame: 24 months ]
    Prostate specific antigen (PSA) progression is defined by the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.

  4. Objective response rate [ Time Frame: 24 months ]
  5. Quality of life [ Time Frame: 24 months ]
    Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)

  6. Peak plasma concentration (Cmax) [ Time Frame: 12 weeks ]
  7. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 12 weeks ]
  8. T1/2 (Half-life) [ Time Frame: 12 weeks ]
    The time required for the plasma concentration of a drug to be reduced by 50%



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ECOG performance scale 0 - 1.
  • Life expectancy of more than 6 months.
  • Histologically or cytologic confirmed prostate adenocarcinoma without neuroendocrine differentiation or small cell features
  • Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy
  • Evidence of prostate cancer progression by radiographic or PSA criteria
  • Radiological evidence of distant metastatic lesions
  • Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the screening visit
  • 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).
  • Signed and dated informed consent.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

  • 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
  • Prior treatment with enzalutamide, abiraterone, or ketoconazole for prostate cancer
  • History of seizure or any conditions that may predispose to seizure
  • Concurrent or planned treatment with corticosteroids, medications known to have seizure potential, or herbal products known to decrease PSA levels
  • Planned to initiate any other anti-tumor therapies during the study
  • Less than 4 weeks from the last clinical trial
  • Evidence of brain metastasis or primary tumors
  • Clinically significant cardiovascular diseases
  • Abuse of alcohol or drugs
  • Severe concurrent disease, infection, or bone metastasis that, in the judgment of the investigator, would make the patient inappropriate for enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02691975


Contacts
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Contact: Dingwei Ye, M.D. +86-21-64438640 dwyeli@163.com

Locations
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China, Beijing
Beijing Hosptial Recruiting
Beijing, Beijing, China
Contact: Ben Wang, M.D.         
Chinese PLA General Hospital Recruiting
Beijing, Beijing, China
Contact: Xu Zhang, M.D.         
China, Chongqing
Chongqing Cancer Hospital Not yet recruiting
Chongqing, Chongqing, China
Contact: Hong Luo, M.D.         
China, Henan
Henan Cancer Hospital Recruiting
Zhenzhou, Henan, China
Contact: Chaohong He, M.D.         
China, Hunan
Hunan Cancer Hospital Not yet recruiting
Changsha, Hunan, China
Contact: Weiqing Han, M.D.         
China, Jiangsu
Jiangsu Cancer Hospital Recruiting
Nanjing, Jiangsu, China
Contact: Qing Zou, M.D.         
China, Shanghai
Fudan University Shanghai Cancer Center Recruiting
Shanghai, Shanghai, China, 200032
Contact: Dingwei Ye, M.D.    +86-21-64438640    dwyeli@163.com   
Principal Investigator: Dingwei Ye, M.D.         
Huadong Hospital Affiliated to Fudan University Recruiting
Shanghai, Shanghai, China
Contact: Zhongquan Sun, M.D.         
China, Shanxi
The Second Affiliated Hospital of Xi'an Jiaotong University Recruiting
Xi'an, Shanxi, China
Contact: Tie Chong, M.D.         
China, Tianjin
Tianjin Medical University Cancer Institute & Hospital Recruiting
Tianjin, Tianjin, China
Contact: Xin Yao, M.D.         
China, Zhejiang
The Second Affiliated Hospital of Zhejiang University School of Medicine Recruiting
Hangzhou, Zhejiang, China
Contact: Chuanjun Du, M.D.         
Zhejiang Cancer Hospital Recruiting
Hangzhou, Zhejiang, China
Contact: Shaoxing Zhu, M.D.         
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Investigators
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Principal Investigator: Dingwei Ye, M.D. Fudan University

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Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT02691975    
Other Study ID Numbers: SHR3680-001
First Posted: February 25, 2016    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases