Trial of QLH12016 in Patients With Metastatic Castration Resistant Prostate Cancer

Exclusion Criteria

• •1. Metastasis of the central nervous system (CNS), leptomeningeal metastasis or spinal cord compression caused by metastasis (exceeding the physiological alternative dose) requiring hormone treatment
• •2. Radiation therapy that has irradiated more than 25% of the bone marrow was performed within 4 weeks. Palliative radiation therapy is allowed to alleviate pain caused by bone metastasis during the study period
• •3. Treatment with similar drugs
• •4. Received other clinical trial drugs or major surgeries within 4 weeks (sufficient wound healing after major surgeries must undergo clinical evaluation)
• •5. Systemic anti-cancer treatment within the first 2 weeks (bicalutamide, Mitomycin C or Nitroso urea 6 weeks, enzalutamide 5 weeks, and abiolone 4 weeks). Medications that maintain castration are allowed.
• •6. Planned bilateral orchiectomy during the study treatment
• •7. Inability to swallow, chronic diarrhea and bowel obstruction, or other factors affecting drug administration and absorption
• •8. Epilepsy or disease that can induce seizure within 12 months (including a history of transient ischemic attack, stroke, brain trauma with disorders of consciousness, etc.)
• •9. History of psychotropic substance abuse, alcoholism, or drug use, neurological or mental disorders, including dementia or hepatic encephalopathy
• •10. Any of the following conditions occurs within 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure (New York Heart Association III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism or other thromboembolic diseases with clinical significance
• •11. Any of the following conditions within 6 months: congenital long QT syndrome, torsade de pointes ventricular tachycardia, arrhythmia (including persistent ventricular tachyarrhythmia and Ventricular fibrillation), left anterior half block (double vessel block) or persistent arrhythmia above NCI-CTCAE grade 2, Atrial fibrillation of any level (in the case of Asymptomatic isolated Atrial fibrillation, grade ≥ 2)
• •12. Cardiovascular diseases under poor control, including angina pectoris, pulmonary hypertension or serious cardiac rhythm or conduction abnormalities
• •13. QTcF\>450 ms
• •14. Active, uncontrolled bacterial, fungal, or viral infections, including but not limited to: 1) Active hepatitis B virus (HBV), hepatitis C virus (HCV) infected persons (hepatitis B surface antigen \[HBsAg\] positive or hepatitis B core antibody \[HBcAb\] positive, HBV DNA virus copy number ≥ 500 IU/mL, HCV antibody positive and HCV RNA higher than the detection limit of the analysis method); 2) Syphilis required treatment; 3) History of congenital immunodeficiency or organ transplantation, or HIV (HIV) positive
• •15. Clinically uncontrollable third space effusion, such as pleural effusion, peritoneal effusion, pericardial effusion, etc. that cannot be controlled by drainage or other measures and cannot be included in the group according to the judgment of the investigator
• •16. Other malignant tumors within 5 years (excluding cured basal cell skin cancer, papillary thyroid cancer, etc.)
• •17. Concomitant diseases seriously endangering the safety of the subject or affect the completion of the study, such as hypertension (systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg) that cannot be controlled by two or more antihypertensive drugs, diabetes not well controlled, etc
• •18. History of hypertensive crisis or hypertensive encephalopathy
• •19. Allergy to any study drug component
• •20. Gastrointestinal perforation, gastrointestinal or non gastrointestinal fistula, or abdominal abscess within 6 months
• •21. Any life-threatening bleeding event within 3 months, including the need for blood transfusion treatment, surgery or local treatment, and continuous medication treatment
• •22. Subjects who may increase research related risks, interfere with the interpretation of research results, or are deemed unsuitable for inclusion by the researcher