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

Study Overview
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Brief Summary
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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.

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

Conditions
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Metastatic Castration Resistant Prostate Cancer

Intervention / Treatment
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* Drug: HC-1119


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (those who meet all of the following are eligible): Voluntarily participated in the study, with understanding of relevant study procedures and signed informed consent form; Male , ≥18 years old; With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma; With evidence of metastatic disease (such as bone scan and CT/MRI results); 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); Castrate levels of testosterone (< 50 ng/dl) at screening; Bilateral orchiectomy or ongoing androgen deprivation therapy with effective GnRH analogues; Estimated life expectancy > 6 months; ECOG performance status ≤ 1; Laboratory tests must meet the following criteria: 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; 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); Coagulation: INR < 1.5. Exclusion Criteria (those who meet any one of the following are ineligible): Ongoing toxicity ( ≥ Grade 2 toxicity) from previous treatments; 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; History of allergies, or known hypersensitivity to components of the investigational drug; Brain metastases; Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer); History of organ transplants HIV seropositive; Past medical history of seizures or serious CNS diseases; History of unexplained coma; Family history of seizures; History of traumatic brain injury; History of medication or drug abuse; Patients with severe cardiovascular diseases, including those with myocardial infarction, arterial thrombosis, unstable angina, or clinical symptomatic heart failure within the past 6 months; 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; Medications that lower the seizure threshold must be used during the study; Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within the past 4 weeks; Treatment with ketoconazole within the past 4 weeks; 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); Participated in other clinical trials within 1 month prior to enrollment; Subjects is determined by the investigator to be unsuitable for this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dose group<br>Drug name L:HC-1119 Dosage: 40 mg, 80 mg, 160 mg, and 200 mg | Drug: HC-1119<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities(DLT) | Safety measures | From the first dose of the study to the 12th week after dose | 
| Number of patients with adverse events | Safety measures | From the first dose of the study to the 12th week after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum drug concentration(Cmax) | Single-dose and repeated-dose | From the first dose of the study to the 12th week after dose | 
| Time of maximum drug concentration(Tmax) | Single-dose and repeated-dose | From the first dose of the study to the 12th week after dose | 
| Area under curve from time 0 to 24h (AUC0-24h) | Single-dose and repeated-dose | From the first dose of the study to the 12th week after dose | 
| Maximal PSA Response Rate | Percentage of patients with > 50% decrease in PSA levels from baseline during the 12-week treatment period | From the first dose of the study to the 12th week after dose | 
| Response rate of prostate specific antigen (PSA) | Percentage of patients with > 50% decrease in PSA levels from baseline at weeks 6, 8, 10, and 12. | From the first dose of the study to the 12th week after dose |