A Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of HC-1119 in Patients.

A Phase I Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of HC-1119 in Patients With Metastatic Castration-Resistant Prostate Cancer.

This is a phase I study evaluating tolerability, pharmacokinetics, and preliminary efficacy of HC-1119 in patients with metastatic castration-resistant prostate cancer. The study objective is to study the tolerability, safety, and dose-limiting toxicities (DLT) of HC-1119 in patients with mCRPC.

Inclusion Criteria (those who meet all of the following are eligible):

1. Voluntarily participated in the study, with understanding of relevant study procedures and signed informed consent form;

2. Male , ≥18 years old;

3. With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma;

4. With evidence of metastatic disease (such as bone scan and CT/MRI results);

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: Serum 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 disease progression defined by PCWG2 with 2 or more new metastatic lesions on bone scan);

6. Castrate levels of testosterone (< 50 ng/dl) at screening;

7. Bilateral orchiectomy or ongoing androgen deprivation therapy with effective GnRH analogues;

8. Estimated life expectancy > 6 months;

9. ECOG performance status ≤ 1;

10. Laboratory tests must meet the following criteria:

    1. Routine Blood Test: hemoglobin (Hb) ≥ 90 g/L (no blood transfusion within the last 14 days); 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.

Exclusion Criteria (those who meet any one of the following are ineligible):

1. Ongoing toxicity ( ≥ Grade 2 toxicity) from previous treatments;
2. Clinically 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;
3. History of allergies, or known hypersensitivity to components of the investigational drug;
4. Brain metastases;
5. Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer);
6. History of organ transplants
7. HIV seropositive;
8. Past medical history of seizures or serious CNS diseases;
9. History of unexplained coma;
10. Family history of seizures;
11. History of traumatic brain injury;
12. History of medication or drug abuse;
13. Patients with severe cardiovascular diseases, including those with myocardial infarction, arterial thrombosis, unstable angina, or clinical symptomatic heart failure within the past 6 months;
14. Uncontrolled hypertension (systolic ≥ 160 mmHg or diastolic ≥ 100 mmHg). Patients with a history of hypertension is eligible if his blood pressure is controlled with antihypertensives;
15. Medications that lower the seizure threshold must be used during the study;
16. Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within the past 4 weeks;
17. Treatment with ketoconazole within the past 4 weeks;
18. 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 enzalutamide, SHR3680, proxalutamide, and ARN509);
19. Participated in other clinical trials within 1 month prior to enrollment;
20. Subjects is determined by the investigator to be unsuitable for this study.