A Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of HC-1119 in Patients.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: dose group Drug name L:HC-1119 Dosage: 40 mg, 80 mg, 160 mg, and 200 mg |
Drug: HC-1119
oral
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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;
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Male , ≥18 years old;
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With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma;
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With evidence of metastatic disease (such as bone scan and CT/MRI results);
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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);
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Castrate levels of testosterone (< 50 ng/dl) at screening;
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Bilateral orchiectomy or ongoing androgen deprivation therapy with effective GnRH analogues;
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Estimated life expectancy > 6 months;
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ECOG performance status ≤ 1;
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Laboratory tests must meet the following criteria:
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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;
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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);
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Coagulation: INR < 1.5.
Exclusion Criteria (those who meet any one of the following are ineligible):
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Ongoing toxicity ( ≥ Grade 2 toxicity) from previous treatments;
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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;
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History of allergies, or known hypersensitivity to components of the investigational drug;
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Brain metastases;
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Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer);
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History of organ transplants
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HIV seropositive;
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Past medical history of seizures or serious CNS diseases;
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History of unexplained coma;
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Family history of seizures;
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History of traumatic brain injury;
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History of medication or drug abuse;
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Patients with severe cardiovascular diseases, including those with myocardial infarction, arterial thrombosis, unstable angina, or clinical symptomatic heart failure within the past 6 months;
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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;
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Medications that lower the seizure threshold must be used during the study;
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Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within the past 4 weeks;
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Treatment with ketoconazole within the past 4 weeks;
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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);
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Participated in other clinical trials within 1 month prior to enrollment;
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Subjects is determined by the investigator to be unsuitable for this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hinova Pharmaceuticals Inc. | Chengdu | Sichuan | China | 610041 |
Sponsors and Collaborators
- Hinova Pharmaceuticals Inc.
- West China Hospital
Investigators
- Principal Investigator: Feng Bi, professor, West China Hospital
- Principal Investigator: Li Zheng, professor, West China Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HC-1119-01