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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03850795




Registration number
NCT03850795
Ethics application status
Date submitted
20/02/2019
Date registered
22/02/2019
Date last updated
13/06/2024

Titles & IDs
Public title
HC-1119 Versus Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Scientific 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)
Secondary ID [1] 0 0
HC1119-CS-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer Metastatic 0 0
Castration-resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HC-1119
Treatment: Drugs - Enzalutamide

Experimental: HC-1119 - Oral dose of 80 mg/day

Active comparator: enzalutamide - Oral dose of 160 mg/day


Treatment: Drugs: HC-1119
oral once daily 80 mg

Treatment: Drugs: Enzalutamide
oral once daily 160 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
PSA decline of =50% from baseline
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Radiographic Progression-free Survival (rPFS)
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Week 24
Secondary outcome [4] 0 0
Safety and Tolerability (based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0)
Timepoint [4] 0 0
Week 24

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
Accrual to date
Final
104
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 0 0
Icon Cancer Care Gold Coast - Southport
Recruitment hospital [2] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [3] 0 0
Affinity Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
4215 - Southport
Recruitment postcode(s) [2] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
Austria
State/province [8] 0 0
Linz
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Denmark
State/province [11] 0 0
Aalborg
Country [12] 0 0
Denmark
State/province [12] 0 0
Odense C
Country [13] 0 0
Finland
State/province [13] 0 0
Helsinki
Country [14] 0 0
Finland
State/province [14] 0 0
Oulu
Country [15] 0 0
Finland
State/province [15] 0 0
Seinäjoki
Country [16] 0 0
Finland
State/province [16] 0 0
Tampere
Country [17] 0 0
France
State/province [17] 0 0
Hauts-de-Seine
Country [18] 0 0
France
State/province [18] 0 0
Le Mans
Country [19] 0 0
France
State/province [19] 0 0
Lille Cedex
Country [20] 0 0
France
State/province [20] 0 0
Lyon
Country [21] 0 0
France
State/province [21] 0 0
Pierre-Bénite
Country [22] 0 0
France
State/province [22] 0 0
Saint-Mandé
Country [23] 0 0
Germany
State/province [23] 0 0
Baden-Württemberg
Country [24] 0 0
Germany
State/province [24] 0 0
Bonn
Country [25] 0 0
Germany
State/province [25] 0 0
Tübingen
Country [26] 0 0
Germany
State/province [26] 0 0
Wuppertal
Country [27] 0 0
Italy
State/province [27] 0 0
Umbria
Country [28] 0 0
Italy
State/province [28] 0 0
Verona
Country [29] 0 0
Netherlands
State/province [29] 0 0
Friesland
Country [30] 0 0
Netherlands
State/province [30] 0 0
Gelderland
Country [31] 0 0
Netherlands
State/province [31] 0 0
Noord-Brabant
Country [32] 0 0
Netherlands
State/province [32] 0 0
Zuid-Holland
Country [33] 0 0
Poland
State/province [33] 0 0
Slaskie
Country [34] 0 0
Poland
State/province [34] 0 0
Wielkopolskie
Country [35] 0 0
Poland
State/province [35] 0 0
Lublin
Country [36] 0 0
Poland
State/province [36] 0 0
Siedlce
Country [37] 0 0
Poland
State/province [37] 0 0
Warszawa
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Barnaul
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Ivanovo
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Obninsk
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Omsk
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Saint Petersburg
Country [43] 0 0
Spain
State/province [43] 0 0
Córdoba
Country [44] 0 0
Spain
State/province [44] 0 0
Lugo
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Málaga
Country [47] 0 0
Spain
State/province [47] 0 0
Sevilla
Country [48] 0 0
Spain
State/province [48] 0 0
Valencia
Country [49] 0 0
United Kingdom
State/province [49] 0 0
South Humberside
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Belfast
Country [51] 0 0
United Kingdom
State/province [51] 0 0
London
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Northwood

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hinova Pharmaceuticals USA, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03850795
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03850795