- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02446405
Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET)
Randomised Phase 3 Trial of Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer: ENZAMET
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Chris O'Brien Lifehouse
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Coffs Harbour, New South Wales, Australia, 2450
- Coffs Harbour Health Campus
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Concord, New South Wales, Australia, 2139
- Concord Cancer Centre - Concord Repatriation General Hospital
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Darlinghurst, New South Wales, Australia, 2010
- St Vincent's Hospital Sydney
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Kingswood, New South Wales, Australia, 2747
- Nepean Cancer Care Centre
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Kogarah, New South Wales, Australia, 2217
- St. George Hospital
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Orange, New South Wales, Australia, 2800
- Central West Cancer Services
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Port Macquarie, New South Wales, Australia, 2444
- Port Macquarie Base Hospital
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Randwick, New South Wales, Australia, 2031
- Prince of Wales Hospital
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St Leonards, New South Wales, Australia, 2065
- Genesis Care North Shore
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Tamworth, New South Wales, Australia, 2340
- Tamworth Rural Referral Hospital
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Tweed Heads, New South Wales, Australia, 2485
- The Tweed Hospital
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Wagga Wagga, New South Wales, Australia, 2650
- Riverina Cancer Care Centre
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Wahroonga, New South Wales, Australia, 2076
- Sydney Adventist Hospital
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Wollongong, New South Wales, Australia, 2500
- Wollongong Hospital
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Northern Territory
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Tiwi, Northern Territory, Australia, 0810
- Royal Darwin Hospital
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Queensland
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Birtinya, Queensland, Australia, 4575
- Sunshine Coast University Hospital
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Douglas, Queensland, Australia, 4814
- Townsville Hospital
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Herston, Queensland, Australia, 4006
- Royal Brisbane and Women's Hospital
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Southport, Queensland, Australia, 4215
- Gold Coast University Hospital
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Woolloongabba, Queensland, Australia, 4102
- Princess Alexandra Hospital
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South Australia
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Adelaide, South Australia, Australia, 5000
- Royal Adelaide Hospital
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Bedford Park, South Australia, Australia, 5042
- Flinders Medical Centre
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Kurralta Park, South Australia, Australia, 5037
- Adelaide Cancer Centre - Ashford Cancer Care Centre
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Tasmania
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Hobart, Tasmania, Australia, 7000
- Royal Hobart Hospital
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Victoria
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Bendigo, Victoria, Australia
- Bendigo Hospital
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Bentleigh East, Victoria, Australia, 3165
- Monash Cancer Centre Moorabbin
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East Melbourne, Victoria, Australia, 3002
- Peter MacCallum Cancer Centre - East Melbourne
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Fitzroy, Victoria, Australia, 3065
- St. Vincents Hospital Melbourne
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Frankston, Victoria, Australia, 3199
- Peninsula South Eastern Haematology & Oncology Group- Peninsula Oncology Centre
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Geelong, Victoria, Australia, 3220
- University Hospital Geelong
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Heidelberg, Victoria, Australia, 3084
- Austin Hospital
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Malvern, Victoria, Australia, 3144
- Australian Urology Associates
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Melbourne, Victoria, Australia
- Eastern Health Box Hill Hospital
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Shepparton, Victoria, Australia, 3630
- Goulburn Valley Health
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Wodonga, Victoria, Australia, 3690
- Border Medical Oncology
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Sir Charles Gairdner Hospital
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Perth, Western Australia, Australia, 6000
- Fiona Stanley Hospital (formerly Royal Perth Hospital)
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Alberta
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Calgary, Alberta, Canada, T2V 1P9
- Prostate Cancer Institute - Southern Alberta Institute of Urology
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Edmonton, Alberta, Canada, AB T6G 1Z2
- Cross Cancer Institute
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British Columbia
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Surrey, British Columbia, Canada, BC V3V 1Z2
- BCCA - Fraser Valley Cancer Center
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Vancouver, British Columbia, Canada, V5Z 4E6
- BCCA Vancouver Centre
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Manitoba
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Winnipeg, Manitoba, Canada
- CancerCare Manitoba
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New Brunswick
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Fredericton, New Brunswick, Canada, NB E3B 5N5
- Horizon Health Network - Dr Everett Chalmers Hospital
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Saint John, New Brunswick, Canada, NB E2L 4L4
- Saint John Regional Hospital
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Nova Scotia
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Halifax, Nova Scotia, Canada, NS B3H 2Y9
- QEII Health Sciences Centre, Capital District Health Authority
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Ontario
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Cambridge, Ontario, Canada, ON N1R 7S6
- Cambridge Memorial Hospital
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Hamilton, Ontario, Canada, L8V 5C2
- Juravinski Cancer Centre
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Kingston, Ontario, Canada, ON K7L 5P9
- Cancer Centre of Southeastern Ontario at Kingston General Hospital
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London, Ontario, Canada, N6A 5W9
- London Regional Cancer Program
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Oshawa, Ontario, Canada, ON L1G 2B9
- Lakeridge Health Oshawa
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Ottawa, Ontario, Canada, ON K1H 8L6
- Ottawa Hospital Cancer Centre
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Sault Ste. Marie, Ontario, Canada, P6B 0A8
- Algoma District Cancer Program Sault Area Hospital
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Thunder Bay, Ontario, Canada, ON P7B 6V4
- Thunder Bay Regional Health Sciences Centre
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Toronto, Ontario, Canada, ON M5G 2M9
- University Health Network - Princess Margaret Hospital
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Quebec
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Montreal, Quebec, Canada, H2L 4M1
- Hôpital Notre-Dame
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Québec City, Quebec, Canada, QC G1R 2J6
- CHUQ-Pavillon Hotel-Dieu de Quebec
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Saskatchewan
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Regina, Saskatchewan, Canada, S4T 7T1
- Allan Blair Cancer Centre
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Saskatoon, Saskatchewan, Canada, S7N 4H4
- Saskatoon Cancer Centre
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Dublin, Ireland, DUBLIN 4
- St Vincent's University Hospital
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Dublin, Ireland, Dublin 8
- St James Hospital
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Dublin, Ireland, Dublin 18
- Beacon Private Hospital
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Dublin, Ireland, Dublin 7
- Mater Misercordiae University Hospital
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Dublin, Ireland, Dublin 7
- Mater Private Hospital
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Galway, Ireland
- Galway University Hospital
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Tallaght, Ireland, Dublin 24
- Adelaide and Meath Hospital - National Children's Hospital
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Waterford, Ireland
- University Hospital Waterford
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Dublin
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Beaumont, Dublin, Ireland, Dublin 9
- Beaumont Hospital
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Auckland, New Zealand
- Auckland City Hospital
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Christchurch, New Zealand, 8140
- Christchurch Hospital
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Hamilton, New Zealand, 3204
- Waikato Hospital
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London, United Kingdom, SE1 9RT
- Guys and St Thomas Hospital
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London, United Kingdom, SW3 6JJ
- Royal Marsden Hospital
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London, United Kingdom, NW1 2BU
- University College Hospital London
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Southampton, United Kingdom, SO16 6YD
- University Hospital Southampton
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Swindon, United Kingdom, SN3 6BB
- Great Western Hospital
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Cornwall
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Truro, Cornwall, United Kingdom, TR1 3LQ
- Royal Cornwall Hospital
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East Sussex
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Brighton, East Sussex, United Kingdom, BN2 5BE
- Royal Sussex Hospital
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Kent
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Canterbury, Kent, United Kingdom, CT1 3NG
- Kent and Canterbury Hospital
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Scotland
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Aberdeen, Scotland, United Kingdom, AB25 2ZN
- Aberdeen Royal Infirmary
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Wales
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Cardiff, Wales, United Kingdom, CF14 2TL
- Velindre Cancer Centre
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana Farber Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Men starting first line androgen deprivation therapy for metastatic prostate cancer.
Inclusion criteria:
- Male aged 18 or older with metastatic adenocarcinoma of the prostate
- Target or non-target lesions according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1
- Adequate bone marrow function: Haemoglobin (Hb) ≥100g/L and White Cell Count (WCC) ≥ 4.0 x 109/L and platelets ≥100 x 109/L.
- 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
- Adequate renal function: calculated creatinine clearance > 30 ml/min (Cockcroft-Gault)
- 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.
- Study treatment both planned and able to start within 7 days after randomisation.
- Willing and able to comply with all study requirements, including treatment and required assessments
- Has completed baseline Health-Related Quality of Life (HRQL) questionnaires UNLESS is unable to complete because of limited literacy or vision
- Signed, written, informed consent
Exclusion Criteria:
- Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
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.
- Life expectancy of less than 12 months.
- 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).
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.
- 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;
- Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.
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.
- Prior cytotoxic chemotherapy for prostate cancer, but up to 2 cycles of docetaxel chemotherapy for metastatic disease is permitted.
- Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
|
Active Comparator: 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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival Time
Time Frame: 3 years
|
the interval from the date of randomisation to date of death.
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Prostate specific antigen progression free survival time
Time Frame: 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 |
3 years
|
Clinical progression free survival time
Time Frame: 3 years
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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
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3 years
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Adverse events
Time Frame: 3 years
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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
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3 years
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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))
Time Frame: 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
|
3 years
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Healthcare resource cost-effectiveness (incremental cost effectiveness ratio)
Time Frame: 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
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3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Christopher Sweeney, Dana Farber Cancer Institute and ANZUP
- Study Chair: Ian Davis, ANZUP and Eastern Health Box Hill Hospital
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ANZUP 1304
- ACTRN12614000110684 (Other Identifier: Australian New Zealand Clinical Trials Registry (ANZCTR))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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