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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.

Tracking Information
First Submitted Date  ICMJE February 17, 2016
First Posted Date  ICMJE February 25, 2016
Last Update Posted Date October 29, 2019
Actual Study Start Date  ICMJE April 12, 2016
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2016)
  • 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
  • Radiological progression-free survival [ Time Frame: 24 months ]
    For Phase 2 portion of study
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2016)
  • Number of participants with treatment-related adverse events [ Time Frame: 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 [ Time Frame: 12 weeks ]
  • 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.
  • Objective response rate [ Time Frame: 24 months ]
  • Quality of life [ Time Frame: 24 months ]
    Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)
  • Peak plasma concentration (Cmax) [ Time Frame: 12 weeks ]
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: 12 weeks ]
  • T1/2 (Half-life) [ Time Frame: 12 weeks ]
    The time required for the plasma concentration of a drug to be reduced by 50%
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of SHR3680 in Metastatic Castration-Resistant Prostate Cancer Patients
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hormone Refractory Prostate Cancer
  • Metastatic Prostate Carcinoma
Intervention  ICMJE Drug: SHR3680
SHR3680 is administrated orally, qd, 28 days as one cycle. Patients may continue SHR3680 until disease progression or unacceptable toxicity.
Study Arms  ICMJE Experimental: SHR3680
Tablet
Intervention: Drug: SHR3680
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 25, 2019)
200
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2016)
140
Estimated Study Completion Date  ICMJE June 1, 2020
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dingwei Ye, M.D. +86-21-64438640 dwyeli@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02691975
Other Study ID Numbers  ICMJE SHR3680-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jiangsu HengRui Medicine Co., Ltd.
Study Sponsor  ICMJE Jiangsu HengRui Medicine Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dingwei Ye, M.D. Fudan University
PRS Account Jiangsu HengRui Medicine Co., Ltd.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP