A study of HC-1119 versus Enzalutamide in Metastatic Castration Resistant Prostate Cancer
- Conditions
- Metastatic Castration-Resistant Prostate CancerMedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001144-22-NL
- Lead Sponsor
- Hinova Pharmaceuticals (USA), Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 430
1. Age 18 or older and willing and able to give informed consent.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
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.
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.
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:
a. Patient is non-fertile (orchiectomy) or has a female partner of non-childbearing potential (i.e., post-menopausal, 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 340
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 < 3,000/ µL, or 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 invention 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 Cockroft-Gault equation at the Screening visit.
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, biologics, cyproterone acetate or agents with anti tumor activity against prostate cancer (i.e. Radium 223, ketoconazole) within four weeks of enrollment (Day 1 visit).
12. History of progression of prostate cancer while on ketoconazole.
13. Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents) within 4 weeks of enrollment (Day 1 visit).
14. 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).
15. Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone, galeterone, seviteronel) or blocks the AR (e.g., apalutamide, darolutamide, enzalutamide, proxalutamide).
16. Participation in a previous clinical trial of HC-1119.
17. Use of an investigational agent within four weeks of enrollment (Day 1 visit).
18. Radiation therapy for treatment of the primary tumor within three weeks of enrollment (Day 1 visit).
19. Radionuclide therapy for treatment of metastasis.
20. 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 patients with history of congestive heart failure NYHA class 3 or 4 in the past, 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 fibrillation, torsades de pointes)
• History of Mobitz II third degree heart block without a permanent pacemaker in place
• Bradycardia as indicated by a heart rate of < 50 beats per minute on the Scree
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method