Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer

Phase 3

Active, not recruiting

• Conditions: Prostatic Neoplasms
• Interventions: Drug: NSAA; Drug: Enzalutamide; Drug: LHRHA or Surgical Castration

• Registration Number: NCT02446405
• Lead Sponsor: University of Sydney

Brief Summary

The purpose of this study is to determine the effectiveness of enzalutamide, versus a conventional non-steroidal anti androgen (NSAA), when combined with a luteinizing hormone releasing hormone analog (LHRHA) or surgical castration, as first line androgen deprivation therapy (ADT) for newly diagnosed metastatic prostate cancer.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2015-05-04
• Study First Submitted QC: 2015-05-13
• Study First Posted: 2015-05-18
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 1125

Inclusion Criteria

Not provided

Exclusion Criteria

1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components

2. History of

   • seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).
   • loss of consciousness or transient ischemic attack within 12 months of randomization
   • significant cardiovascular disease within the last 3 months including: myocardial infarction, unstable angina, congestive heart failure, ongoing arrhythmias of Grade >2 [National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.03], thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.

3. Life expectancy of less than 12 months.

4. History of another malignancy within 5 years prior to randomisation, except for either non- melanomatous carcinoma of the skin or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta and low grade T1 tumours).

5. Concurrent illness, including severe infection that might jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety

   a. Human Immunodeficiency Virus (HIV)-infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant enzalutamide.

6. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;

7. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.

8. Prior ADT for prostate cancer (including bilateral orchidectomy), except in the following settings:

   • Started less than 12 weeks prior to randomisation AND Prostate Specific Antigen (PSA) is stable or falling. The 12 weeks starts from whichever of the following occurs earliest: first dose of oral anti- androgen, LHRHA, or surgical castration.
   • In the adjuvant setting, where the completion of adjuvant hormonal therapy was more than 12 months prior to randomisation AND the total duration of hormonal treatment did not exceed 24 months. For depot preparations, hormonal therapy is deemed to have started with the first dose and to have been completed when the next dose would otherwise have been due, e.g. 12 weeks after the last dose of depot goserelin 10.8mg.

9. Prior cytotoxic chemotherapy for prostate cancer, but up to 2 cycles of docetaxel chemotherapy for metastatic disease is permitted.

10. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional NSAA	LHRHA or Surgical Castration	Conventional NSAA, by mouth until clinical disease progression or prohibitive toxicity. All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.
Conventional NSAA	NSAA	Conventional NSAA, by mouth until clinical disease progression or prohibitive toxicity. All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.
Enzalutamide	LHRHA or Surgical Castration	Enzalutamide is 160 mg daily, by mouth, until clinical disease progression or prohibitive toxicity. All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.
Enzalutamide	Enzalutamide	Enzalutamide is 160 mg daily, by mouth, until clinical disease progression or prohibitive toxicity. All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.

Primary Outcome Measures

Name	Time	Method
Overall Survival Time	3 years	the interval from the date of randomisation to date of death.

Secondary Outcome Measures

Name	Time	Method
Adverse events	3 years	The NCI Common Terminology Criteria for Adverse Events version 4 (CTCAE v4.03) will be used to classify and grade the intensity of adverse events during study treatment
Healthcare resource cost-effectiveness (incremental cost effectiveness ratio)	3 years	Information on the following areas of health-care resource usage will be collected: hospitalisations, visits to health professionals, and medications Australian unit costs will be applied to the resource usage data to estimate the incremental cost of the addition of enzalutamide to standard treatment
Clinical progression free survival time	3 years	the interval from the date of randomisation to the date of first clinical evidence of disease progression or death from any cause, whichever occurs first, or the date of last known follow-up without clinical progression
Health-related quality of life (EORTC Core Quality of Life Questionnaire (QLQ C-30), Quality of Life Questionnaire for Prostate Cancer (PR-25), Euroqol 5 item preference-based measure of health (EQ-5 D-5L))	3 years	HRQL will be reported by participants using the EORTC core quality of life questionnaire (QLQ C-30) and prostate cancer specific module (PR-25). The EQ-5D-5L will be used to derive utility scores suitable for quality adjusted survival analyses
Prostate specific antigen progression free survival time	3 years	the interval from the date of randomisation to the date of first evidence of PSA progression, clinical progression, or death from any cause, whichever occurs first, or the date of last known follow-up without PSA progression; PSA progression is defined as: a rise in PSA by more than 25% AND more than 2ng/mL

Trial Locations

Locations (82)

BCCA Vancouver Centre; 🇨🇦 Vancouver, British Columbia, Canada

Australian Urology Associates; 🇦🇺 Malvern, Victoria, Australia

Austin Hospital; 🇦🇺 Heidelberg, Victoria, Australia

Border Medical Oncology; 🇦🇺 Wodonga, Victoria, Australia

Mater Private Hospital; 🇮🇪 Dublin, Ireland

CHUQ-Pavillon Hotel-Dieu de Quebec; 🇨🇦 Québec City, Quebec, Canada

Galway University Hospital; 🇮🇪 Galway, Ireland

St Vincent's University Hospital; 🇮🇪 Dublin, Ireland

Mater Misercordiae University Hospital; 🇮🇪 Dublin, Ireland

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Beaumont Hospital; 🇮🇪 Beaumont, Dublin, Ireland

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Kent and Canterbury Hospital; 🇬🇧 Canterbury, Kent, United Kingdom

Fiona Stanley Hospital (formerly Royal Perth Hospital); 🇦🇺 Perth, Western Australia, Australia

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, New South Wales, Australia

St. Vincents Hospital Melbourne; 🇦🇺 Fitzroy, Victoria, Australia

Saint John Regional Hospital; 🇨🇦 Saint John, New Brunswick, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

University Health Network - Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Concord Cancer Centre - Concord Repatriation General Hospital; 🇦🇺 Concord, New South Wales, Australia

Coffs Harbour Health Campus; 🇦🇺 Coffs Harbour, New South Wales, Australia

Nepean Cancer Care Centre; 🇦🇺 Kingswood, New South Wales, Australia

St Vincent's Hospital Sydney; 🇦🇺 Darlinghurst, New South Wales, Australia

St. George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Central West Cancer Services; 🇦🇺 Orange, New South Wales, Australia

Port Macquarie Base Hospital; 🇦🇺 Port Macquarie, New South Wales, Australia

Genesis Care North Shore; 🇦🇺 St Leonards, New South Wales, Australia

Prince of Wales Hospital; 🇦🇺 Randwick, New South Wales, Australia

Tamworth Rural Referral Hospital; 🇦🇺 Tamworth, New South Wales, Australia

Riverina Cancer Care Centre; 🇦🇺 Wagga Wagga, New South Wales, Australia

Wollongong Hospital; 🇦🇺 Wollongong, New South Wales, Australia

The Tweed Hospital; 🇦🇺 Tweed Heads, New South Wales, Australia

Sydney Adventist Hospital; 🇦🇺 Wahroonga, New South Wales, Australia

Sunshine Coast University Hospital; 🇦🇺 Birtinya, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Gold Coast University Hospital; 🇦🇺 Southport, Queensland, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Herston, Queensland, Australia

Townsville Hospital; 🇦🇺 Douglas, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

Adelaide Cancer Centre - Ashford Cancer Care Centre; 🇦🇺 Kurralta Park, South Australia, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Bendigo Hospital; 🇦🇺 Bendigo, Victoria, Australia

Monash Cancer Centre Moorabbin; 🇦🇺 Bentleigh East, Victoria, Australia

Peter MacCallum Cancer Centre - East Melbourne; 🇦🇺 East Melbourne, Victoria, Australia

Peninsula South Eastern Haematology & Oncology Group- Peninsula Oncology Centre; 🇦🇺 Frankston, Victoria, Australia

University Hospital Geelong; 🇦🇺 Geelong, Victoria, Australia

Goulburn Valley Health; 🇦🇺 Shepparton, Victoria, Australia

Prostate Cancer Institute - Southern Alberta Institute of Urology; 🇨🇦 Calgary, Alberta, Canada

BCCA - Fraser Valley Cancer Center; 🇨🇦 Surrey, British Columbia, Canada

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

Horizon Health Network - Dr Everett Chalmers Hospital; 🇨🇦 Fredericton, New Brunswick, Canada

Juravinski Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

Lakeridge Health Oshawa; 🇨🇦 Oshawa, Ontario, Canada

Cambridge Memorial Hospital; 🇨🇦 Cambridge, Ontario, Canada

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada

Ottawa Hospital Cancer Centre; 🇨🇦 Ottawa, Ontario, Canada

Hôpital Notre-Dame; 🇨🇦 Montreal, Quebec, Canada

Thunder Bay Regional Health Sciences Centre; 🇨🇦 Thunder Bay, Ontario, Canada

Algoma District Cancer Program Sault Area Hospital; 🇨🇦 Sault Ste. Marie, Ontario, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Saskatoon Cancer Centre; 🇨🇦 Saskatoon, Saskatchewan, Canada

Beacon Private Hospital; 🇮🇪 Dublin, Ireland

St James Hospital; 🇮🇪 Dublin, Ireland

University Hospital Waterford; 🇮🇪 Waterford, Ireland

Adelaide and Meath Hospital - National Children's Hospital; 🇮🇪 Tallaght, Ireland

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Royal Cornwall Hospital; 🇬🇧 Truro, Cornwall, United Kingdom

Christchurch Hospital; 🇳🇿 Christchurch, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, New Zealand

Royal Sussex Hospital; 🇬🇧 Brighton, East Sussex, United Kingdom

University College Hospital London; 🇬🇧 London, United Kingdom

Aberdeen Royal Infirmary; 🇬🇧 Aberdeen, Scotland, United Kingdom

Velindre Cancer Centre; 🇬🇧 Cardiff, Wales, United Kingdom

Guys and St Thomas Hospital; 🇬🇧 London, United Kingdom

University Hospital Southampton; 🇬🇧 Southampton, United Kingdom

Great Western Hospital; 🇬🇧 Swindon, United Kingdom

Royal Marsden Hospital; 🇬🇧 London, United Kingdom

QEII Health Sciences Centre, Capital District Health Authority; 🇨🇦 Halifax, Nova Scotia, Canada

Eastern Health Box Hill Hospital; 🇦🇺 Melbourne, Victoria, Australia

Royal Darwin Hospital; 🇦🇺 Tiwi, Northern Territory, Australia