a study evaluating tolerability, pharmacokinetics, and preliminary efficacy of hc-1119 in patients.

Conditions: Metastatic Castration Resistant Prostate Cancer

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.


Eligibility criteria:
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.