Castration-resistant Prostate Cancer, Prostate Cancer Metastatic
Conditions
Keywords
HC-1119, enzalutamide
Brief summary
This study is a multinational Phase 3, randomized, double-blind, non-inferiority, efficacy and safety study of oral HC-1119 (80 mg/day) versus enzalutamide (160 mg/day) in asymptomatic or mildly symptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC). The following assessment of prostate cancer status will be collected during the course of the trial: soft tissue disease on computed tomography (CT) scan or on magnetic resonance imaging (MRI), bone disease on radionuclide bone scans, FACT-P and EQ-5D, Brief Fatigue Inventory, and PSA. Throughout the study, safety and tolerability will be assessed by the recording of adverse events, monitoring of vital signs and physical examinations, safety laboratory evaluations, and 12-lead electrocardiograms (ECGs). Blood samples for population pharmacokinetics for HC-1119 and enzalutamide and related metabolites will be collected.
Detailed description
This study is a multinational Phase 3, randomized, double-blind, non-inferiority, efficacy and safety study of oral HC-1119 (80 mg/day) versus enzalutamide (160 mg/day) in asymptomatic or mildly symptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Patients must not have been previously treated with next generation AR-Inhibitors or Androgen-biosynthesis Inhibitors, or prior progression on ketoconazole. The following assessments of prostate cancer status will be collected during the course of the trial: soft tissue disease on computed tomography (CT) scan or on magnetic resonance imaging (MRI), bone disease on radionuclide bone scans, FACT-P and EQ-5D, Brief Fatigue Inventory, and PSA. Radiographic disease progression is defined by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) for soft tissue disease, or the appearance of two or more new bone lesions on bone scan. Throughout the study, safety and tolerability will be assessed by the recording of adverse events, monitoring of vital signs and physical examinations, safety laboratory evaluations, and 12-lead electrocardiograms (ECGs). Blood samples for population pharmacokinetics for HC-1119 and enzalutamide and related metabolites will be collected pre-dose on Day 1 and prior to dosing on Days 8 (Week 2), 15 (Week 3) and 22 (Week 4), 29 (Week 5), 57 (Week 9), 85 (Week 13) and Day 169 (Week 25). Blood samples for calculating a 24 hour pharmacokinetic profile of HC-1119 and enzalutamide and related metabolites will be collected in a subset of 24 Caucasian (non-Chinese) patients on Day 1 and at steady state in week 9. Patients will have a safety follow-up visit 30 days after their last dose of study drug or prior to initiation of any new therapy, or an investigational agent, whichever occurs first.
Interventions
DRUGHC-1119
oral once daily 80 mg
DRUGEnzalutamide
oral once daily 160 mg
Sponsors
Hinova Pharmaceuticals USA, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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's judgment. 3. Ongoing ADT with a 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 GnRH analogue or antagonist therapy for the duration of the trial. 5. Serum testosterone level \< 1.7 nmol/L (50 ng/dL) at the Screening visit. 6. Patients receiving bisphosphonate or denosumab therapy must have been on stable doses for at least four weeks (from Day 1 visit). 7. Progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on ADT as defined in eligibility criterion #3: 1. PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 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) 2. Soft tissue disease progression defined by RECIST 1.1 3. 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. 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: 1. Patient is non-fertile (orchiectomy) or has a female partner of non-childbearing potential (i.e., post-menopausal, surgically sterilized, hysterectomy) 2. Patient and his female partner 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
Subjects must NOT meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Week 24 | To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by overall response rate (ORR) by RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA decline of ≥50% from baseline | Week 24 | To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by decline of ≥50% from baseline |
| Radiographic Progression-free Survival (rPFS) | Week 24 | To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by radiographic progression-free survival (rPFS) |
| Overall Survival (OS) | Week 24 | To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by overall survival (OS) |
| Safety and Tolerability (based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0) | Week 24 | To determine the safety and tolerability of orally administrated HC-1119 as compared to enzalutamide based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
Countries
Australia, Austria, Canada, Denmark, Finland, France, Germany, Italy, Netherlands, Poland, Russia, Spain, United Kingdom, United States
Outcome results
None listed