Metastatic Castration Resistant Prostate Cancer
Conditions
Brief summary
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.
Interventions
DRUGHC-1119
oral
Sponsors
West China Hospital
Hinova Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities(DLT) | From the first dose of the study to the 12th week after dose | Safety measures |
| Number of patients with adverse events | From the first dose of the study to the 12th week after dose | Safety measures |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum drug concentration(Cmax) | From the first dose of the study to the 12th week after dose | Single-dose and repeated-dose |
| Time of maximum drug concentration(Tmax) | From the first dose of the study to the 12th week after dose | Single-dose and repeated-dose |
| Area under curve from time 0 to 24h (AUC0-24h) | From the first dose of the study to the 12th week after dose | Single-dose and repeated-dose |
| Maximal PSA Response Rate | From the first dose of the study to the 12th week after dose | Percentage of patients with \> 50% decrease in PSA levels from baseline during the 12-week treatment period |
| Response rate of prostate specific antigen (PSA) | From the first dose of the study to the 12th week after dose | Percentage of patients with \> 50% decrease in PSA levels from baseline at weeks 6, 8, 10, and 12. |
Countries
China
Outcome results
None listed