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

NCT03850795 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: HC1119-CS-03
• Study Type: interventional
• Target: 104
• Locations: 13 countries
• Sites: 57

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.

Conditions

Prostate Cancer Metastatic; Castration-resistant Prostate Cancer

Keywords

HC-1119; enzalutamide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• PSA decline of ≥50% from baseline

  Week 24

• Radiographic Progression-free Survival (rPFS)

  Week 24

• Overall Survival (OS)

  Week 24

• Safety and Tolerability (based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0)

  Week 24

Study Arms (2)

HC-1119

EXPERIMENTAL

Oral dose of 80 mg/day

Drug: HC-1119

enzalutamide

ACTIVE COMPARATOR

Oral dose of 160 mg/day

Drug: Enzalutamide

Interventions

HC-1119 DRUG

oral once daily 80 mg

HC-1119

Enzalutamide DRUG

oral once daily 160 mg

enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older and willing and able to give informed consent.
• 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.
• Serum testosterone level \< 1.7 nmol/L (50 ng/dL) at the Screening visit.
• 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 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..
• No prior cytotoxic chemotherapy for prostate cancer.
• Asymptomatic or mildly symptomatic from prostate cancer.
• ECOG performance status of 0-1 per the Investigators' clinical assessment
• Estimated life expectancy of ≥ 6 months

You may not qualify if:

• Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment.
• Known or suspected brain metastasis or active leptomeningeal disease.
• 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 \< 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).
• 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.
• 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)\] / \[72 \* Serum Creatinine (mg/dL)\]
• Albumin \< 30 g/L (3.0 g/dL) at the Screening visit, no therapeutic invention within 14 days before screening.
• History of another malignancy within the previous two years other than curatively treated non-melanomatous skin cancer.
• Treatment with flutamide within four weeks of enrollment (Day 1 visit).
• Treatment with bicalutamide or nilutamide within six weeks of enrollment (Day 1 visit).
• Treatment with 5-α reductase inhibitors (finasteride, dutasteride), estrogens within four weeks of enrollment (Day 1 visit).
• 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).
• Participation in a previous clinical trial of HC-1119.

Sponsors & Collaborators

• Hinova Pharmaceuticals USA, Inc.: lead

Study Sites (58)

Urology Center of Colorado, 2777 Mile High Stadium Circle

Denver, Colorado, 80211, United States

Location

Urologic Surgeons of Washington

Washington D.C., District of Columbia, 20036, United States

Location

First Urology PSC, 101 Hospital Boulevard

Jeffersonville, Indiana, 47130, United States

Location

Clinical Research Solutions PC

Middleburg Heights, Ohio, 44130, United States

Location

MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Keystone Urology Specialists

Lancaster, Pennsylvania, 17604, United States

Location

Urology San Antonio Stone Oak, 18915 Meisner Drive

San Antonio, Texas, 78258-4223, United States

Location

Providence Regional Cancer System

Lacey, Washington, 98503, United States

Location

Icon Cancer Care Gold Coast

Southport, Queensland, 4215, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, 5037, Australia

Location

Affinity Clinical Research

Nedlands, 6009, Australia

Location

Kepler Universitätsklinikum Linz

Linz, 4020, Austria

Location

Fe/Male Health Centre

Oakville, Ontario, L6H 3P1, Canada

Location

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, J1H5N4, Canada

Location

Aalborg Universitetshospital

Aalborg, 9000, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Helsinki University Hospital Comprehensive Cancer Center - PPDS

Helsinki, 00290, Finland

Location

Oulun Yliopistollinen Sairaala

Oulu, 90220, Finland

Location

Seinäjoen Keskussairaala

Seinäjoki, 60220, Finland

Location

Tampereen yliopistollinen sairaala

Tampere, 33521, Finland

Location

Hopital Foch

Suresnes, Hauts-de-Seine, 92151, France

Location

Centre Jean Bernard Clinique Victor Hugo

Le Mans, 72000, France

Location

CHRU Lille

Lille, 59037, France

Location

Centre Léon Berard

Lyon, 69008, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Hopital d'Instruction des Armées de Begin

Saint-Mandé, 94160, France

Location

Urologische Studienpraxis

Nürtingen, Baden-Wurttemberg, 72622, Germany

Location

Universitätsklinikum Bonn

Bonn, 53127, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

UroGynZentrum Wall

Wuppertal, 42103, Germany

Location

Azienda Ospedaliera S Maria Di Terni

Terni, Umbria, Italy

Location

Azienda Ospedaliera Universitaria Integrata Di Verona

Verona, 37126, Italy

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, Gelderland, 6532 SZ, Netherlands

Location

Catharina Hospital

Eindhoven, North Brabant, 5623 EJ, Netherlands

Location

Antonius Ziekenhuis

Sneek, Provincie Friesland, 8601 ZK, Netherlands

Location

Hagaziekenhuis

The Hague, South Holland, 2545 AA, Netherlands

Location

Clinical Research Center Spolka z Ograniczona

Poznan, Greater Poland Voivodeship, 60-848, Poland

Location

NZOZ Centrum Urologiczne Sp zoo

Mysłowice, Silesian Voivodeship, 41-400, Poland

Location

Onko-Centrum Sp. z o.o.

Lublin, 20-250, Poland

Location

Urologica Praktyka Lekarska Adam Marcheluk

Siedlce, 08-110, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Altay Regional Oncology Center

Barnaul, 656045, Russia

Location

Ivanovo Regional Oncology Dispensary

Ivanovo, 153040, Russia

Location

Federal State Institution Medical Radiology Research Center

Obninsk, 249036, Russia

Location

Clinical Oncology Dispensary

Omsk, 644013, Russia

Location

First St. Petersburg State Medical University n.a. I.P Pavlov

Saint Petersburg, 197022, Russia

Location

GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)

Saint Petersburg, 197758, Russia

Location

Hospital Orkli LLC

Saint Petersburg, 199178, Russia

Location

C.H. Regional Reina Sofia - PPDS

Córdoba, 14004, Spain

Location

Hospital Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Malaga - Hospital Civil

Málaga, 29009, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Diana Princess of Wales Hospital

Grimsby, South Humberside, DN33 2BA, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

Location

Mount Vernon Hospital

Northwood, HA6 2RN, United Kingdom

Location

MeSH Terms

Interventions

enzalutamide

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: February 22, 2019
• Study Start: March 15, 2021
• Primary Completion: June 28, 2024
• Study Completion: June 28, 2024
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4); IT (2); ES (6); FR (6); AU (3); FI (4); DE (4); PL (5); RU (7); GB (4); CA (2); US (8); DK (2)