PROCADE: A Multinational Phase 3, Randomized, Double-Blind, Non-Inferiority, Efficacy and Safety Study of Oral HC-1119 versus Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
- Conditions
- metastatic castration-resistant prostate cancer / prostate cancer1003859710036958
- Registration Number
- NL-OMON55283
- Lead Sponsor
- Hinova Pharmaceuticals (USA), Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 18
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 <= 1.7 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 #2:
a. 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)
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
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 < 3,000/µL, or absolute Absolute neutrophil count < 1,500/µL, or
platelet count < 100,000/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 intervention within 14 days of the hematologic
laboratory values obtained at the Screening visit).
5. Total bilirubin, alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) > 2.5 times the upper limit of normal at the Screening
visit; no therapeutic invention within 14 days before screening
6. 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)]
7. Albumin < 30 g/L (3.0 g/dL) at the Screening visit, no therapeutic invention
within 14 days before screening.
8. History of another malignancy within the previous two years other than
curatively treated
non-melanomatous skin cancer.
9. Treatment with flutamide within four weeks of enrollment (Day 1 visit).
10. Treatment with bicalutamide or nilutamide within six weeks of enrollment
(Day 1 visit).
11. Treatment with 5-a reductase inhibitors (finasteride, dutasteride),
estrogens within four weeks of enrollment (Day 1 visit).
12. Treatment with systemic biologic therapy for prostate cancer (other than
approved bone targeted agents) within 4 weeks of enrollment (Day 1 visit).
13. 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).
14. Prior use, or participation in a clinical trial, of an agent that blocks
androgen synthesis (e.g., abiraterone) or blocks the androgen receptor (AR)
(e.g., apalutamide, darolutamide, enzalutamide, proxalutamide).
15. Participation in a previous clinical trial of HC-1119.
16. Use of an investigational agent within four weeks of enrollment (Day 1
visit).
17. Radiation therapy for treatment of the primary tumor within three weeks of
enrollment (Day 1 visit).
18. Radionuclide therapy(Radium 223) for treatment of metastasis within four
weeks of enrollment (Day 1 visit).
19. Clinically significant cardiovascular disease or condition including:
- Myocardial infarction within six months
- Uncontrolled angina within three months
- Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
with
history of congestive heart failure NYHA class 3 or 4, unless a screening
echocardiogram or multi-gated acquisition scan (MUGA) performed within three
months results in a left ventricular ejection fraction that is >= 45%
- History of clinically significant ventricular arrhythmias (e.g., ventricular
tachycardia, ventricular fibrilla
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall Response Rate (ORR) of HC-1119-treated and the enzalutamide group by<br /><br>RECIST v1.1 in patients with measurable soft tissue disease within 24 weeks</p><br>
- Secondary Outcome Measures
Name Time Method