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

NCT ID: NCT02691975

Last Updated: 2020-05-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 197 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-12
• Study Completion Date: 2021-06-01

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.

Conditions

Hormone Refractory Prostate Cancer; Metastatic Prostate Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SHR3680

Tablet

Group Type: EXPERIMENTAL

SHR3680

Intervention Type: DRUG

SHR3680 is administrated orally, qd, 28 days as one cycle. Patients may continue SHR3680 until disease progression or unacceptable toxicity.

Interventions

SHR3680

SHR3680 is administrated orally, qd, 28 days as one cycle. Patients may continue SHR3680 until disease progression or unacceptable toxicity.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dingwei Ye, M.D.

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Beijing Hosptial

Beijing, Beijing Municipality, China

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, China

Henan Cancer Hospital

Zhenzhou, Henan, China

Hunan Cancer Hospital

Changsha, Hunan, China

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Huadong Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, China

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 35241087 (View on PubMed)

Other Identifiers

SHR3680-001

Identifier Type: -

Identifier Source: org_study_id