metastatic castration-resistant prostate cancer / prostate cancer
Conditions
Interventions
Enzalutamide capsules plus HC-1119-matching placebo or HC-1119 capsules plus
enzalutamide-matching placebo will be administered in the same manner to
patients by oral administration.
Sponsors
Hinova Pharmaceuticals (USA), Inc.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Subjects must meet the following inclusion criteria: 1. Age 18 or older and willing and able to give informed consent. 2. Histologically or cytologically confirmed adenocarcinoma of the prostate without significant and relevant neuroendocrine differentiation or small cell features, per investigator judgement. 3. Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) analogue, antagonist or bilateral orchiectomy (i.e., surgical or medical castration). 4. For patients who have not had a bilateral orchiectomy, there must be a plan to maintain effective GnRHanalogue or antagonist therapy for the duration of the trial. 5. Serum testosterone level = 1 week between each determination. Patients who received an anti-androgen agent must have progression after withdrawal (>= 4 weeks since last flutamide or >= 6 weeks since last bicalutamide or nilutamide). The PSA value at the Screening visit should be >= 2 µg/L (2 ng/mL) b. Soft tissue disease progression defined by RECIST 1.1 c. Bone disease progression defined by PCWG3 with two or more new lesions on bone scan 8. Metastatic disease documented by measurable soft tissue disease by CT/MRI per RECIST 1.1. criteria. Patients are allowed to have any metastatic disease (i.e. bone metastasis) as long as they also have measurable soft tissue lesions per RECIST 1.1. 9. No prior cytotoxic chemotherapy for prostate cancer. 10. Asymptomatic or mildly symptomatic from prostate cancer. 11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 per the Investigators* clinical assessment 12. Estimated life expectancy of >= 6 months 13. Able to swallow the study drug and comply with study requirements 14. All sexually active patients are required to use a condom as well as meet 1 of the following: a. Patient is non-fertile (orchiectomy) or has a female partner of non-childbearing potential (i.e., postmenopausal, surgically sterilized, hysterectomy) b. Patient and his female partner use must agree to use an adequate contraceptive method from the first day of dosing until 3 months after the last dose to prevent pregnancies. Adequate contraceptive method is defined as: i. Established use of oral, injected, or implanted hormonal methods of contraception. ii. Placement of an intra-uterine device or intra-uterine system. iii. Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. iv. Tubal ligation for at least 6 months prior to screening. 15. Male patient engaged in sexual activity with a pregnant female is required to use a condom from the first day of dosing until 3 months after the last dose of treatment with study drugs
Exclusion criteria
Exclusion criteria: Subjects must NOT meet any of the following exclusion criteria: 1. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment. 2. Known or suspected brain metastasis or active leptomeningeal disease. 3. Regular daily use of opiate analgesics for pain from prostate cancer within four weeks of enrollment (Day 1 visit). 4. WBC count 2.5 times the upper limit of normal at the Screening visit; no therapeutic invention within 14 days before screening 6. Creatinine clearance = 45% - History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrilla
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) of HC-1119-treated and the enzalutamide group by RECIST v1.1 in patients with measurable soft tissue disease within 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| The key secondary efficacy outcome is: • the proportion of patients showing a PSA decline of >= 50% from baseline at 24 weeks Other (exploratory) secondary efficacy outcomes include: • Radiographic Progression-free Survival (rPFS) of the HC- 1119-treated and the enzalutamide groups • Overall Survival (OS) of the HC-1119-treated and the enzalutamide groups • Duration of response of the HC-1119-treated and the enzalutamide groups • Time to first skeletal-related event of the HC-1119-treated and the enzalutamide groups • Time to PSA progression and PSA response >=90% of the HC-1119-treated and the enzalutamide groups • FACT-P and EQ-5D data summarized descriptively of the HC-1119-treated and the enzalutamide groups • Brief Fatigue Inventory at baseline, 13 weeks and 25 weeks for the HC-1119-treated and the enzalutamide groups. Safety: The safety of HC-1119 will be assessed by the frequency of serious adverse events (AEs), frequency and severity of AEs, frequency of study drug discontinuation due to AEs, as well as the frequency of new clinically significant changes in physical exam findings, vital signs, laboratory values, and ECGs. Pharmacokinetics: Plasma concentrations of HC-1119 and enzalutamide and metabolites for both population pharmacokinetics and PK/PD analysis will be collected at various time points as described in more detail in the Study Schedule of Activities (SoA). A full pharmacokinetic (PK) profile at steady state for both HC-1119 and enzalutamide and related metabolites will be obtained in a subset of 24 Caucasian (non-Chinese) patients (12 patients receiving HC-1119 and 12 patients receiving enzalutamide). | — |
Countries
Netherlands
Outcome results
None listed