HC-1119 Versus Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

  • STATUS
    Recruiting
  • End date
    May 13, 2023
  • participants needed
    430
  • sponsor
    Hinova Pharmaceuticals USA, Inc.
Updated on 13 May 2022

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.

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.

Details
Condition Prostate Cancer Metastatic, Castration-resistant Prostate Cancer
Treatment Enzalutamide, HC-1119
Clinical Study IdentifierNCT03850795
SponsorHinova Pharmaceuticals USA, Inc.
Last Modified on13 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Subjects must meet the following inclusion criteria
Age 18 or older and willing and able to give informed consent
Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the Screening visit
Histologically or cytologically confirmed adenocarcinoma of the prostate without significant and relevant neuroendocrine differentiation or small cell features, per investigator's judgment
Ongoing ADT with a GnRH analogue, antagonist or bilateral orchiectomy (i.e., surgical or medical castration)
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
Asymptomatic or mildly symptomatic from prostate cancer
Patients receiving bisphosphonate or denosumab therapy must have been on stable doses for at least four weeks (from Day 1 visit)
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
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)
Soft tissue disease progression defined by RECIST 1.1
Bone disease progression defined by PCWG3 with two or more new lesions on bone scan
Metastatic disease documented by measurable soft tissue disease by CT/MRI per RECIST
No prior cytotoxic chemotherapy for prostate cancer
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
ECOG performance status of 0-1 per the Investigators' clinical assessment
RECIST 1.1
Able to swallow the study drug and comply with study requirements
All sexually active patients are required to use a condom as well as meet 1 of the
following
Estimated life expectancy of ≥ 6 months
Patient is non-fertile (orchiectomy) or has a female partner of non-childbearing potential (i.e., post-menopausal, surgically sterilized, hysterectomy)
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
Established use of oral, injected, or implanted hormonal methods of contraception
iv. Tubal ligation for at least 6 months prior to screening
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
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 exclusion criteria
Known or suspected brain metastasis or active leptomeningeal disease
Participation in a previous clinical trial of HC-1119
Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
investigator, would make the patient inappropriate for enrollment
Regular daily use of opiate analgesics for pain from prostate cancer within four weeks
of enrollment (Day 1 visit)
WBC count < 3,000/µL, or absolute neutrophil count < 1,500/µL, or platelet count <
Treatment with flutamide within four weeks of enrollment (Day 1 visit)
000/µL, or hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit (NOTE: patients
may not have received any growth factors or blood transfusions or any therapeutic
invention within 14 days of the hematologic laboratory values obtained at the
Screening visit)
Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >
5 times the upper limit of normal at the Screening visit; no therapeutic invention
within 14 days before screening
Use of an investigational agent within four weeks of enrollment (Day 1 visit)
Creatinine clearance < 30 mL/min as calculated using the Cockcroft-Gault equation at
the Screening visit. Creatinine Clearance (mL/min) = [[140-Age (years)] Weight (kg)]
[72 Serum Creatinine (mg/dL)]
Clinically significant cardiovascular disease or condition
Albumin < 30 g/L (3.0 g/dL) at the Screening visit, no therapeutic invention within 14
days before screening
History of seizure or any condition that may predispose to seizure
History of another malignancy within the previous two years other than curatively
treated non-melanomatous skin cancer
Major surgery within four weeks prior to enrollment (Day 1 visit)
Treatment with bicalutamide or nilutamide within six weeks of enrollment (Day 1
visit)
Have known active tuberculosis
Treatment with 5-α reductase inhibitors (finasteride, dutasteride), estrogens within
Known hypersensitivity to HC-1119, enzalutamide, or any of the excipients
four weeks of enrollment (Day 1 visit)
Rare hereditary problems of fructose intolerance due to sorbitol
Treatment with systemic biologic therapy for prostate cancer (other than approved bone
targeted agents) within four weeks of enrollment (Day 1 visit)
Use of herbal products that may have hormonal anti-prostate cancer activity and/or are
known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater
than the equivalent of 10 mg of prednisone/prednisolone per day within four weeks of
enrollment (Day 1 visit)
Prior use, or participation in a clinical trial, of an agent that blocks androgen
synthesis (e.g., abiraterone) or blocks the AR (e.g., apalutamide, darolutamide
enzalutamide, proxalutamide)
Radiation therapy for treatment of the primary tumor within three weeks of enrollment
(Day 1 visit)
Radionuclide therapy (Radium 223) for treatment of metastasis within four weeks of
enrollment (Day 1 visit)
Treatment with strong CYP2C8 inhibitors and inducers, CYP3A4 inducers, medications
which are known to prolong the QT interval (see Appendix C)
Conditions that predispose subjects to increased risk for falls or fractures according
to the discretion of the Investigator
Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer
disease within last three months)
Have active infection with HBV measured by hepatitis B surface antigen (HBsAg) test
HCV measured by RNA test and HIV measured by antibody test
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