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

Phase 1

• Conditions: Hormone Refractory Prostate Cancer; Metastatic Prostate Carcinoma
• Interventions: Drug: SHR3680

• Registration Number: NCT02691975
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2016-02-17
• Study First Submitted QC: 2016-02-22
• Study First Posted: 2016-02-25
• Study Start: 2016-04-12
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-12
• Last Update Posted: 2020-05-13
• Primary Completion: 2020-12-01
• Study Completion: 2021-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 197

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SHR3680	SHR3680	Tablet

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Objective response rate	24 months
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.
Quality of life	24 months	Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)
Peak plasma concentration (Cmax)	12 weeks
Number of participants with treatment-related adverse events	24 months	Adverse events are assessed by CTCAE v4.0
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%

Trial Locations

Locations (12)

Beijing Hosptial; 🇨🇳 Beijing, Beijing, China

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

Chongqing Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

Henan Cancer Hospital; 🇨🇳 Zhenzhou, Henan, China

Jiangsu Cancer Hospital; 🇨🇳 Nanjing, Jiangsu, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

The Second Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shanxi, China

Huadong Hospital Affiliated to Fudan University; 🇨🇳 Shanghai, Shanghai, China

Tianjin Medical University Cancer Institute & Hospital; 🇨🇳 Tianjin, Tianjin, China

The Second Affiliated Hospital of Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China