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

Metastatic Prostate Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02691975
• Other study ID #: SHR3680-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 12, 2016
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2020
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 197
• Est. completion date: June 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hormone Refractory Prostate Cancer
• Metastatic Prostate Carcinoma
• Prostatic Neoplasms

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Radiological progression-free survival	For Phase 2 portion of study	24 months
Secondary	Number of participants with treatment-related adverse events	Adverse events are assessed by CTCAE v4.0	24 months
Secondary	The percentage of patients reaching at least a 50% reduction in prostate specific antigen (PSA) as compared to baseline at 12 weeks		12 weeks
Secondary	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
Secondary	Objective response rate		24 months
Secondary	Quality of life	Brief Pain Inventory (Short Form), Functional Assessment of Cancer Therapy-Prostate (v4.0)	24 months
Secondary	Peak plasma concentration (Cmax)		12 weeks
Secondary	Area under the plasma concentration versus time curve (AUC)		12 weeks
Secondary	T1/2 (Half-life)	The time required for the plasma concentration of a drug to be reduced by 50%	12 weeks