Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer

NCT ID: NCT02446405

Last Updated: 2025-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2027-06-30

Brief Summary

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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

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Conditions

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Prostatic Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Stratification factors:

1. High volume disease (yes versus no), characterised as:

* 4 or more bone metastases, one of which is outside the vertebral column and pelvis AND/OR
* Visceral metastases (e.g. lung, pleura, liver, adrenal and others) Lymph node involvement or bladder invasion do NOT qualify as visceral disease.
2. Study site
3. Concomitant "anti-resorptive" therapy to delay skeletal related events when commencing ADT
4. Co-morbidities according to the Adult Co-morbidity Evaluation (ACE-27: 0-1 vs 2-3)
5. Early use of docetaxel defined as use of docetaxel in conjunction with initiation of ADT.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Enzalutamide

Intervention Type DRUG

LHRHA or Surgical Castration

Intervention Type DRUG

Conventional 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.

Group Type ACTIVE_COMPARATOR

NSAA

Intervention Type DRUG

LHRHA or Surgical Castration

Intervention Type DRUG

Interventions

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Enzalutamide

Intervention Type DRUG

NSAA

Intervention Type DRUG

LHRHA or Surgical Castration

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male aged 18 or older with metastatic adenocarcinoma of the prostate
2. Target or non-target lesions according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1
3. Adequate bone marrow function: Haemoglobin (Hb) ≥100g/L and White Cell Count (WCC) ≥ 4.0 x 109/L and platelets ≥100 x 109/L.
4. Adequate liver function: Alanine transaminase (ALT) \< 2 x Upper Limit of Normal (ULN) and bilirubin \< 1.5 x ULN, (or if bilirubin is between 1.5-2 x ULN, they must have a normal conjugated bilirubin). If liver metastases are present ALT must be \< 5 x ULN
5. Adequate renal function: calculated creatinine clearance \> 30 ml/min (Cockcroft-Gault)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients with performance status 2 are only eligible if the decline in performance status is due to metastatic prostate cancer.
7. Study treatment both planned and able to start within 7 days after randomisation.
8. Willing and able to comply with all study requirements, including treatment and required assessments
9. Has completed baseline Health-Related Quality of Life (HRQL) questionnaires UNLESS is unable to complete because of limited literacy or vision
10. Signed, written, informed consent

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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Australian and New Zealand Urogenital and Prostate Cancer Trials Group

OTHER

Sponsor Role collaborator

Cancer Trials Ireland

NETWORK

Sponsor Role collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christopher Sweeney

Role: STUDY_CHAIR

Dana Farber Cancer Institute and ANZUP

Ian Davis

Role: STUDY_CHAIR

ANZUP and Eastern Health Box Hill Hospital

Locations

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Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status

Coffs Harbour Health Campus

Coffs Harbour, New South Wales, Australia

Site Status

Concord Cancer Centre - Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Nepean Cancer Care Centre

Kingswood, New South Wales, Australia

Site Status

St. George Hospital

Kogarah, New South Wales, Australia

Site Status

Central West Cancer Services

Orange, New South Wales, Australia

Site Status

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Genesis Care North Shore

St Leonards, New South Wales, Australia

Site Status

Tamworth Rural Referral Hospital

Tamworth, New South Wales, Australia

Site Status

The Tweed Hospital

Tweed Heads, New South Wales, Australia

Site Status

Riverina Cancer Care Centre

Wagga Wagga, New South Wales, Australia

Site Status

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Site Status

Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

Royal Darwin Hospital

Tiwi, Northern Territory, Australia

Site Status

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Site Status

Townsville Hospital

Douglas, Queensland, Australia

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Gold Coast University Hospital

Southport, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status

Adelaide Cancer Centre - Ashford Cancer Care Centre

Kurralta Park, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Bendigo Hospital

Bendigo, Victoria, Australia

Site Status

Monash Cancer Centre Moorabbin

Bentleigh East, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre - East Melbourne

East Melbourne, Victoria, Australia

Site Status

St. Vincents Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status

Peninsula South Eastern Haematology & Oncology Group- Peninsula Oncology Centre

Frankston, Victoria, Australia

Site Status

University Hospital Geelong

Geelong, Victoria, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Australian Urology Associates

Malvern, Victoria, Australia

Site Status

Eastern Health Box Hill Hospital

Melbourne, Victoria, Australia

Site Status

Goulburn Valley Health

Shepparton, Victoria, Australia

Site Status

Border Medical Oncology

Wodonga, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Fiona Stanley Hospital (formerly Royal Perth Hospital)

Perth, Western Australia, Australia

Site Status

Prostate Cancer Institute - Southern Alberta Institute of Urology

Calgary, Alberta, Canada

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

BCCA - Fraser Valley Cancer Center

Surrey, British Columbia, Canada

Site Status

BCCA Vancouver Centre

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Horizon Health Network - Dr Everett Chalmers Hospital

Fredericton, New Brunswick, Canada

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

QEII Health Sciences Centre, Capital District Health Authority

Halifax, Nova Scotia, Canada

Site Status

Cambridge Memorial Hospital

Cambridge, Ontario, Canada

Site Status

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Site Status

London Regional Cancer Program

London, Ontario, Canada

Site Status

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Site Status

Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Site Status

Algoma District Cancer Program Sault Area Hospital

Sault Ste. Marie, Ontario, Canada

Site Status

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, Canada

Site Status

University Health Network - Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Hôpital Notre-Dame

Montreal, Quebec, Canada

Site Status

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

Site Status

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Site Status

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Site Status

Beaumont Hospital

Beaumont, Dublin, Ireland

Site Status

Beacon Private Hospital

Dublin, , Ireland

Site Status

St Vincent's University Hospital

Dublin, , Ireland

Site Status

Mater Misercordiae University Hospital

Dublin, , Ireland

Site Status

Mater Private Hospital

Dublin, , Ireland

Site Status

St James Hospital

Dublin, , Ireland

Site Status

Galway University Hospital

Galway, , Ireland

Site Status

Adelaide and Meath Hospital - National Children's Hospital

Tallaght, , Ireland

Site Status

University Hospital Waterford

Waterford, , Ireland

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Waikato Hospital

Hamilton, , New Zealand

Site Status

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom

Site Status

Royal Sussex Hospital

Brighton, East Sussex, United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, Kent, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Site Status

Velindre Cancer Centre

Cardiff, Wales, United Kingdom

Site Status

University College Hospital London

London, , United Kingdom

Site Status

Guys and St Thomas Hospital

London, , United Kingdom

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

University Hospital Southampton

Southampton, , United Kingdom

Site Status

Great Western Hospital

Swindon, , United Kingdom

Site Status

Countries

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United States Australia Canada Ireland New Zealand United Kingdom

References

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Armstrong AJ, Azad AA, Conduit C, Haas GP, Bland C, Davis ID. Enzalutamide in metastatic hormone-sensitive prostate cancer: A plain language summary of the ARCHES and ENZAMET follow-up studies. Future Oncol. 2025 Jan;21(1):15-24. doi: 10.1080/14796694.2024.2408101. Epub 2024 Oct 15.

Reference Type DERIVED
PMID: 39404227 (View on PubMed)

Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. doi: 10.1016/S1470-2045(23)00063-3.

Reference Type DERIVED
PMID: 36990608 (View on PubMed)

Stockler MR, Martin AJ, Davis ID, Dhillon HM, Begbie SD, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx GM, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar WR, Pook DW, Reaume MN, Sandhu S, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter DG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP. J Clin Oncol. 2022 Mar 10;40(8):837-846. doi: 10.1200/JCO.21.00941. Epub 2021 Dec 20.

Reference Type DERIVED
PMID: 34928708 (View on PubMed)

Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. doi: 10.1056/NEJMoa1903835. Epub 2019 Jun 2.

Reference Type DERIVED
PMID: 31157964 (View on PubMed)

Davis ID. Answering Questions and Questioning Answers: More Evidence To Guide Decision-making About Chemohormonal Therapy in Metastatic Prostate Cancer. Eur Urol. 2018 Jun;73(6):856-858. doi: 10.1016/j.eururo.2018.02.020. Epub 2018 Mar 7. No abstract available.

Reference Type DERIVED
PMID: 29525541 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://www.anzup.org.au/

Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group.

http://ctc.usyd.edu.au/

University of Sydney, National Health and Medical Research Council (NHMRC) Clinical Trials Centre.

http://www.anzctr.org.au/

Australian New Zealand Clinical Trials Registry (ANZCTR)

Other Identifiers

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ACTRN12614000110684

Identifier Type: OTHER

Identifier Source: secondary_id

ANZUP 1304

Identifier Type: -

Identifier Source: org_study_id

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