Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer

Prostatic Neoplasms Clinical Trial

— ENZAMET  

Official title:

Randomised Phase 3 Trial of Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer: ENZAMET

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02446405
• Other study ID #: ANZUP 1304
• Secondary ID: ACTRN12614000110
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 2014
• Est. completion date: December 2024

Study information

• Verified date: November 2022
• Source: University of Sydney
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1125
• Est. completion date: December 2024
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Men starting first line androgen deprivation therapy for metastatic prostate cancer.

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.

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide

• NSAA

• LHRHA or Surgical Castration

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Monash Cancer Centre Moorabbin	Bentleigh East	Victoria
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Coffs Harbour Health Campus	Coffs Harbour	New South Wales
Australia	Concord Cancer Centre - Concord Repatriation General Hospital	Concord	New South Wales
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Townsville Hospital	Douglas	Queensland
Australia	Peter MacCallum Cancer Centre - East Melbourne	East Melbourne	Victoria
Australia	St. Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	Peninsula South Eastern Haematology & Oncology Group- Peninsula Oncology Centre	Frankston	Victoria
Australia	University Hospital Geelong	Geelong	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Nepean Cancer Care Centre	Kingswood	New South Wales
Australia	St. George Hospital	Kogarah	New South Wales
Australia	Adelaide Cancer Centre - Ashford Cancer Care Centre	Kurralta Park	South Australia
Australia	Australian Urology Associates	Malvern	Victoria
Australia	Eastern Health Box Hill Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Central West Cancer Services	Orange	New South Wales
Australia	Fiona Stanley Hospital (formerly Royal Perth Hospital)	Perth	Western Australia
Australia	Port Macquarie Base Hospital	Port Macquarie	New South Wales
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Goulburn Valley Health	Shepparton	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Genesis Care North Shore	St Leonards	New South Wales
Australia	Tamworth Rural Referral Hospital	Tamworth	New South Wales
Australia	Royal Darwin Hospital	Tiwi	Northern Territory
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Australia	Riverina Cancer Care Centre	Wagga Wagga	New South Wales
Australia	Sydney Adventist Hospital	Wahroonga	New South Wales
Australia	Border Medical Oncology	Wodonga	Victoria
Australia	Wollongong Hospital	Wollongong	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Prostate Cancer Institute - Southern Alberta Institute of Urology	Calgary	Alberta
Canada	Cambridge Memorial Hospital	Cambridge	Ontario
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Horizon Health Network - Dr Everett Chalmers Hospital	Fredericton	New Brunswick
Canada	QEII Health Sciences Centre, Capital District Health Authority	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	Hôpital Notre-Dame	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	CHUQ-Pavillon Hotel-Dieu de Quebec	Québec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program Sault Area Hospital	Sault Ste. Marie	Ontario
Canada	BCCA - Fraser Valley Cancer Center	Surrey	British Columbia
Canada	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
Canada	University Health Network - Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA Vancouver Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Ireland	Beaumont Hospital	Beaumont	Dublin
Ireland	Beacon Private Hospital	Dublin
Ireland	Mater Misercordiae University Hospital	Dublin
Ireland	Mater Private Hospital	Dublin
Ireland	St James Hospital	Dublin
Ireland	St Vincent's University Hospital	Dublin
Ireland	Galway University Hospital	Galway
Ireland	Adelaide and Meath Hospital - National Children's Hospital	Tallaght
Ireland	University Hospital Waterford	Waterford
New Zealand	Auckland City Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Waikato Hospital	Hamilton
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Royal Sussex Hospital	Brighton	East Sussex
United Kingdom	Kent and Canterbury Hospital	Canterbury	Kent
United Kingdom	Velindre Cancer Centre	Cardiff	Wales
United Kingdom	Guys and St Thomas Hospital	London
United Kingdom	Royal Marsden Hospital	London
United Kingdom	University College Hospital London	London
United Kingdom	University Hospital Southampton	Southampton
United Kingdom	Great Western Hospital	Swindon
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall
United States	Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
University of Sydney	Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Canadian Cancer Trials Group, Cancer Trials Ireland

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Ireland,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Time	the interval from the date of randomisation to date of death.	3 years
Secondary	Prostate specific antigen progression free survival time	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
Secondary	Clinical progression free survival time	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	3 years
Secondary	Adverse events	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	3 years
Secondary	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))	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
Secondary	Healthcare resource cost-effectiveness (incremental cost effectiveness ratio)	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	3 years

External Links

•   Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group.
•   Australian New Zealand Clinical Trials Registry (ANZCTR)
•   University of Sydney, National Health and Medical Research Council (NHMRC) Clinical Trials Centre.