a study evaluating enzalutamide pharmacokinetics and pharmacodynamics, and related changes after drug switch

Conditions: Metastatic Castration Resistant Prostate Cancer

Summary: this is a study for evaluating enzalutamide pharmacokinetics and pharmacodynamics, and related changes after drug switch in chinese patients with metastatic castration-resistant prostate cancer. the study primary objective is to evaluate the pharmacokinetic characteristics of enzalutamide in chinese patients with mcrpc.


Eligibility criteria:
inclusion criteria: 1. voluntarily participated in the study, with understanding of and will to comply with relevant study procedures and signed informed consent form; 2. chinese male, ≥ 18 years old; 3. with histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma; 4. with evidence of metastatic lesions (such as bone scan and ct/mri); 5. patients with relapsed, refractory, or progressive disease despite castration (surgery or chemical) or combined androgen deprivation therapy. (progressive disease is defined as 1 or more of the following 3 criteria: psa progression: a minimum of 3 rising psa values with an interval of at least 1 week between determinations, resulting in a final value higher than 50% of the minimum, with a starting psa value \> 2 ng/ml; soft tissue disease progression as defined by recist 1.1; bone progression as defined by pcwg2 with 2 or more new lesions on bone scan); 6. castrate levels of testosterone (\< 50 ng/dl) at screening; bilateral orchiectomy or ongoing androgen deprivation therapy with effective gnrh analogues; 7. ecog performance status ≤1; 8. laboratory tests must meet the following criteria: 1. routine blood test: hemoglobin (hb) ≥ 90g/l (no blood transfusions within 14 days prior to screening); absolute neutrophil count (anc) ≥ 1.5 x 109/l; platelet count (plt) ≥ 80 x 109/l; 2. blood biochemistry: creatinine (cr) ≤ 2 x upper limit of normal (uln), or cr \> 2 x uln but the calculated crcl ≥ 60 ml/min; bilirubin (bil) ≤2 x uln; alanine aminotransferase (alt), aspartate aminotransferase (ast) ≤2.5 x uln (or ≤ 5.0 x uln for patients with liver metastases); 3. coagulation: inr \< 1.5. 9. estimated life expectancy \> 6 months. exclusion criteria: 1. participated in other clinical drug trials within 1 month prior to screening, or the occurrence of toxicity caused by previous treatments that has not been relieved to ≤ grade 2 toxicity (according to ctcae 4.03) prior to enrollment; 2. brain metastases; 3. subjects are excluded if any of the following conditions are met: 1. other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer); 2. history of organ transplants; 3. past medical history of seizures, serious cns diseases, or unexplained coma, family history of seizures, or history of traumatic brain injury; 4. uncontrolled hypertension (systolic ≥ 160 mmhg or diastolic ≥ 100 mmhg) or other serious cardiovascular diseases. (patients with a history of hypertension is eligible if his blood pressure is controlled with antihypertensives); 5. significant gi dysfunction which may affect the intake, transport, or absorption of drug (such as inability to swallow, chronic diarrhea, and bowel obstruction, etc.), or patients with complete gastrectomy; 6. other uncontrolled clinical diseases, including but not limited to: persistent or active infections. 4. subjects are excluded if any of the following conditions regarding past or concomitant medication are met: 1. medications that lower the seizure threshold must be used during the trial; 2. treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within 4 weeks prior to screening; 3. treatment with ketoconazole within 4 weeks prior to screening; 4. previously treated with investigational or approved medications that inhibit testosterone synthesis (such as abiraterone acetate, tak-683, and tak-448) or target testosterone receptors (such as shr3680, proxalutamide, and arn509), except for bicalutamide and flutamide. 5. known hypersensitivity to any ingredient of the study drugs (enzalutamide and hc-1119) or similar drugs; 6. hiv seropositive; 7. history of medication or drug abuse; 8. other conditions that subject is determined by the investigator to be unsuitable for this study.