search
Back to results

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

Primary Purpose

Hormone Refractory Prostate Cancer, Metastatic Prostate Carcinoma

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SHR3680
Sponsored by
Jiangsu HengRui Medicine Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hormone Refractory Prostate Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Beijing Hosptial
  • Chinese PLA General Hospital
  • Chongqing Cancer Hospital
  • Henan Cancer Hospital
  • Hunan Cancer Hospital
  • Jiangsu Cancer Hospital
  • Fudan University Shanghai Cancer Center
  • Huadong Hospital Affiliated to Fudan University
  • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Tianjin Medical University Cancer Institute & Hospital
  • The Second Affiliated Hospital of Zhejiang University School of Medicine
  • Zhejiang Cancer Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SHR3680

Arm Description

Tablet

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)
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
For Phase 2 portion of study

Secondary Outcome Measures

Number of participants with treatment-related adverse events
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 to prostate specific antigen (PSA) progression
Prostate specific antigen (PSA) progression is defined by the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.
Objective response rate
Quality of life
Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)
Peak plasma concentration (Cmax)
Area under the plasma concentration versus time curve (AUC）
T1/2 (Half-life)
The time required for the plasma concentration of a drug to be reduced by 50%

Full Information

First Posted
February 17, 2016
Last Updated
May 12, 2020
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT02691975
Brief Title
A Safety and Efficacy Study of SHR3680 in Metastatic Castration-Resistant Prostate Cancer Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 12, 2016 (Actual)
Primary Completion Date
December 1, 2020 (Anticipated)
Study Completion Date
June 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hormone Refractory Prostate Cancer, Metastatic Prostate Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
197 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SHR3680
Arm Type
Experimental
Arm Description
Tablet
Intervention Type
Drug
Intervention Name(s)
SHR3680
Intervention Description
SHR3680 is administrated orally, qd, 28 days as one cycle. Patients may continue SHR3680 until disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
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
Time Frame
12 weeks
Title
Radiological progression-free survival
Description
For Phase 2 portion of study
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events
Description
Adverse events are assessed by CTCAE v4.0
Time Frame
24 months
Title
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
Title
Time to prostate specific antigen (PSA) progression
Description
Prostate specific antigen (PSA) progression is defined by the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.
Time Frame
24 months
Title
Objective response rate
Time Frame
24 months
Title
Quality of life
Description
Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)
Time Frame
24 months
Title
Peak plasma concentration (Cmax)
Time Frame
12 weeks
Title
Area under the plasma concentration versus time curve (AUC）
Time Frame
12 weeks
Title
T1/2 (Half-life)
Description
The time required for the plasma concentration of a drug to be reduced by 50%
Time Frame
12 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dingwei Ye, M.D.
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Hosptial
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Chongqing Cancer Hospital
City
Chongqing
State/Province
Chongqing
Country
China
Facility Name
Henan Cancer Hospital
City
Zhenzhou
State/Province
Henan
Country
China
Facility Name
Hunan Cancer Hospital
City
Changsha
State/Province
Hunan
Country
China
Facility Name
Jiangsu Cancer Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Huadong Hospital Affiliated to Fudan University
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
The Second Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
State/Province
Shanxi
Country
China
Facility Name
Tianjin Medical University Cancer Institute & Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Facility Name
The Second Affiliated Hospital of Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
Country
China
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35241087
Citation
Qin X, Ji D, Gu W, Han W, Luo H, Du C, Zou Q, Sun Z, He C, Zhu S, Chong T, Yao X, Wan B, Yang X, Bai A, Jin C, Zou J, Ye D. Activity and safety of SHR3680, a novel antiandrogen, in patients with metastatic castration-resistant prostate cancer: a phase I/II trial. BMC Med. 2022 Mar 4;20(1):84. doi: 10.1186/s12916-022-02263-x.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs