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

Prostate Cancer Metastatic Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03850795
• Other study ID #: HC1119-CS-03
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 15, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Hinova Pharmaceuticals USA, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 104
• Est. completion date: December 31, 2024
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 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 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 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 four 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 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

20. Treatment with strong CYP2C8 inhibitors and inducers, CYP3A4 inducers, medications which are known to prolong the QT interval (see Appendix C).

21. History of seizure or any condition that may predispose to seizure.

22. Conditions that predispose subjects to increased risk for falls or fractures according to the discretion of the Investigator.

23. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last three months).

24. Major surgery within four weeks prior to enrollment (Day 1 visit).

25. Have active infection with HBV measured by hepatitis B surface antigen (HBsAg) test, HCV measured by RNA test and HIV measured by antibody test.

26. Have known active tuberculosis.

27. Known hypersensitivity to HC-1119, enzalutamide, or any of the excipients.

28. Rare hereditary problems of fructose intolerance due to sorbitol

Related Conditions & MeSH terms

• Castration-resistant Prostate Cancer
• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Drug:
• HC-1119
oral once daily 80 mg
• Enzalutamide
oral once daily 160 mg

Locations

Country	Name	City	State
Australia	Ashford Cancer Centre Research	Kurralta Park	South Australia
Australia	Affinity Clinical Research	Nedlands
Australia	Icon Cancer Care Gold Coast	Southport	Queensland
Austria	Kepler Universitätsklinikum Linz	Linz
Canada	Fe/Male Health Centre	Oakville	Ontario
Canada	CIUSSS de l'Estrie-CHUS	Sherbrooke	Quebec
Denmark	Aalborg Universitetshospital	Aalborg
Denmark	Odense Universitetshospital	Odense C
Finland	Helsinki University Hospital Comprehensive Cancer Center - PPDS	Helsinki
Finland	Oulun Yliopistollinen Sairaala	Oulu
Finland	Seinäjoen Keskussairaala	Seinäjoki
Finland	Tampereen yliopistollinen sairaala	Tampere
France	Centre Jean Bernard Clinique Victor Hugo	Le Mans
France	CHRU Lille	Lille Cedex
France	Centre Léon Berard	Lyon
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Hopital d'Instruction des Armées de Begin	Saint-Mandé
France	Hopital Foch	Suresnes	Hauts-de-Seine
Germany	Universitätsklinikum Bonn	Bonn
Germany	Urologische Studienpraxis	Nürtingen	Baden-Württemberg
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	UroGynZentrum Wall	Wuppertal
Italy	Azienda Ospedaliera S Maria Di Terni	Terni	Umbria
Italy	Azienda Ospedaliera Universitaria Integrata Di Verona	Verona
Netherlands	Hagaziekenhuis	Den Haag	Zuid-Holland
Netherlands	Catharina Hospital	Eindhoven	Noord-Brabant
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen	Gelderland
Netherlands	Antonius Ziekenhuis	Sneek	Friesland
Poland	Onko-Centrum Sp. z o.o.	Lublin
Poland	NZOZ Centrum Urologiczne Sp zoo	Myslowice	Slaskie
Poland	Clinical Research Center Spolka z Ograniczona	Poznan	Wielkopolskie
Poland	Urologica Praktyka Lekarska Adam Marcheluk	Siedlce
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa
Russian Federation	Altay Regional Oncology Center	Barnaul
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	Federal State Institution Medical Radiology Research Center	Obninsk
Russian Federation	Clinical Oncology Dispensary	Omsk
Russian Federation	First St. Petersburg State Medical University n.a. I.P Pavlov	Saint Petersburg
Russian Federation	GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)	Saint Petersburg
Russian Federation	Hospital Orkli LLC	Saint Petersburg
Spain	C.H. Regional Reina Sofia - PPDS	Córdoba
Spain	Hospital Lucus Augusti	Lugo
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Regional Universitario de Malaga - Hospital Civil	Málaga
Spain	Hospital Universitario Virgen del Rocio - PPDS	Sevilla
Spain	Fundacion Instituto Valenciano de Oncologia	Valencia
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Diana Princess of Wales Hospital	Grimsby	South Humberside
United Kingdom	Royal Marsden Hospital - London	London
United Kingdom	Mount Vernon Hospital	Northwood
United States	MidLantic Urology	Bala-Cynwyd	Pennsylvania
United States	Urology Center of Colorado, 2777 Mile High Stadium Circle	Denver	Colorado
United States	First Urology PSC, 101 Hospital Boulevard	Jeffersonville	Indiana
United States	Providence Regional Cancer System	Lacey	Washington
United States	Keystone Urology Specialists	Lancaster	Pennsylvania
United States	Clinical Research Solutions PC	Middleburg Heights	Ohio
United States	Urology San Antonio Stone Oak, 18915 Meisner Drive	San Antonio	Texas
United States	Urologic Surgeons of Washington	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hinova Pharmaceuticals USA, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Denmark,  Finland,  France,  Germany,  Italy,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by overall response rate (ORR) by RECIST 1.1.	Week 24
Secondary	PSA decline of =50% from baseline	To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by decline of =50% from baseline	Week 24
Secondary	Radiographic Progression-free Survival (rPFS)	To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by radiographic progression-free survival (rPFS)	Week 24
Secondary	Overall Survival (OS)	To determine the efficacy of HC-1119 as compared to enzalutamide as assessed by overall survival (OS)	Week 24
Secondary	Safety and Tolerability (based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0)	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.	Week 24