A Study Evaluating Enzalutamide Pharmacokinetics and Pharmacodynamics, and Related Changes After Drug Switch

A Clinical Study for Evaluating Enzalutamide Pharmacokinetics and Pharmacodynamics, and Related Changes After Drug Switch in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer

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.

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.