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

Hengrui Medicine

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Hormone Refractory Prostate Cancer

Metastatic Prostate Carcinoma

Treatments

Drug: SHR3680

Study type

Interventional

Funder types

Industry

Identifiers

NCT02691975

SHR3680-001

Details and patient eligibility

About

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.

Full 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.

Enrollment

197 patients

Sex

Male

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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