Clinical trial NCT02691975: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hormone Refractory Prostate Cancer
Metastatic Prostate Carcinoma
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-02-25
Enrollment: 197
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: 12 weeks
measure: Radiological progression-free survival
timeFrame: 24 months
Secondary outcomes:
measure: Number of participants with treatment-related adverse events
timeFrame: 24 months
measure: The percentage of patients reaching at least a 50% reduction in prostate specific antigen (PSA) as compared to baseline at 12 weeks
timeFrame: 12 weeks
measure: Time to prostate specific antigen (PSA) progression
timeFrame: 24 months
measure: Objective response rate
timeFrame: 24 months
measure: Quality of life
timeFrame: 24 months
measure: Peak plasma concentration (Cmax)
timeFrame: 12 weeks
measure: Area under the plasma concentration versus time curve (AUC）
timeFrame: 12 weeks
measure: T1/2 (Half-life)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hosptial
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Zhenzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Huadong Hospital Affiliated to Fudan University
state: Shanghai
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Dingwei Ye, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.