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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hormone Refractory Prostate Cancer; Metastatic Prostate Carcinoma
• Intervention / Treatment: Drug: 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: Interventional
• Enrollment (Actual): 197
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Chinese PLA General hospital
    • Beijing, Beijing, China
      • Beijing Hosptial
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing Cancer Hospital
  • Henan
    • Zhenzhou, Henan, China
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China
      • Huadong Hospital affiliated to Fudan University
  • Shanxi
    • Xi'an, Shanxi, China
      • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • The Second Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks
Radiological progression-free survival	For Phase 2 portion of study	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration (Cmax)		12 weeks
Area under the plasma concentration versus time curve (AUC）		12 weeks
T1/2 (Half-life)	The time required for the plasma concentration of a drug to be reduced by 50%	12 weeks
Objective response rate		24 months
Number of participants with treatment-related adverse events	Adverse events are assessed by CTCAE v4.0	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	Prostate specific antigen (PSA) progression is defined by the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.	24 months
Quality of life	Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)	24 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2016
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: February 22, 2016
• First Posted (Estimate): February 25, 2016

Study Record Updates

• Last Update Posted (Actual): May 13, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: SHR3680-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO