ENZAMET: Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer

Sponsor

University of Sydney (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02446405

Collaborator

Australian and New Zealand Urogenital and Prostate Cancer Trials Group (Other), National Health and Medical Research Council, Australia (Other), Cancer Trials Ireland (Other), NCIC Clinical Trials Group (Other)

1,125

Enrollment

Locations

Arms

117

Duration (Months)

13.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Enzalutamide Drug: NSAA Drug: LHRHA or Surgical Castration	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1125 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Stratification factors: 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. Study site Concomitant "anti-resorptive" therapy to delay skeletal related events when commencing ADT Co-morbidities according to the Adult Co-morbidity Evaluation (ACE-27: 0-1 vs 2-3) Early use of docetaxel defined as use of docetaxel in conjunction with initiation of ADT.Stratification factors: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. Study site Concomitant "anti-resorptive" therapy to delay skeletal related events when commencing ADT Co-morbidities according to the Adult Co-morbidity Evaluation (ACE-27: 0-1 vs 2-3) Early use of docetaxel defined as use of docetaxel in conjunction with initiation of ADT.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2014

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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.	Drug: Enzalutamide Drug: LHRHA or Surgical Castration
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.	Drug: NSAA Drug: LHRHA or Surgical Castration

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.

Drug: Enzalutamide

Drug: LHRHA or Surgical Castration

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.

Drug: NSAA

Drug: LHRHA or Surgical Castration

Outcome Measures

Primary Outcome Measures

Overall Survival Time [3 years]

Secondary Outcome Measures

Prostate specific antigen progression free survival time [3 years]
Clinical progression free survival time [3 years]
Adverse events [3 years]
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]
Healthcare resource cost-effectiveness (incremental cost effectiveness ratio) [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
3	Coffs Harbour Health Campus	Coffs Harbour	New South Wales	Australia	2450
4	Concord Cancer Centre - Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
5	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
6	Nepean Cancer Care Centre	Kingswood	New South Wales	Australia	2747
7	St. George Hospital	Kogarah	New South Wales	Australia	2217
8	Central West Cancer Services	Orange	New South Wales	Australia	2800
9	Port Macquarie Base Hospital	Port Macquarie	New South Wales	Australia	2444
10	Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
11	Northern Cancer Institute	St Leonards	New South Wales	Australia	2065
12	Tamworth Rural Referral Hospital	Tamworth	New South Wales	Australia	2340
13	The Tweed Hospital	Tweed Heads	New South Wales	Australia	2485
14	Riverina Cancer Care Centre	Wagga Wagga	New South Wales	Australia	2650
15	Sydney Adventist Hospital	Wahroonga	New South Wales	Australia	2076
16	Wollongong Hospital	Wollongong	New South Wales	Australia	2500
17	Royal Darwin Hospital	Tiwi	Northern Territory	Australia	0810
18	Townsville Hospital	Douglas	Queensland	Australia	4814
19	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4006
20	Nambour General Hospital	Nambour	Queensland	Australia	4560
21	Gold Coast University Hospital	Southport	Queensland	Australia	4215
22	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
23	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
24	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
25	Adelaide Cancer Centre - Ashford Cancer Care Centre	Kurralta Park	South Australia	Australia	5037
26	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
27	Bendigo Hospital	Bendigo	Victoria	Australia
28	Monash Cancer Centre Moorabbin	Bentleigh East	Victoria	Australia	3165
29	Peter MacCallum Cancer Centre - East Melbourne	East Melbourne	Victoria	Australia	3002
30	St. Vincents Hospital Melbourne	Fitzroy	Victoria	Australia	3065
31	Peninsula South Eastern Haematology & Oncology Group- Peninsula Oncology Centre	Frankston	Victoria	Australia	3199
32	University Hospital Geelong	Geelong	Victoria	Australia	3220
33	Austin Hospital	Heidelberg	Victoria	Australia	3084
34	Australian Urology Associates	Malvern	Victoria	Australia	3144
35	Eastern Health Box Hill Hospital	Melbourne	Victoria	Australia
36	Goulburn Valley Health	Shepparton	Victoria	Australia	3630
37	Border Medical Oncology	Wodonga	Victoria	Australia	3690
38	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
39	Fiona Stanley Hospital (formerly Royal Perth Hospital)	Perth	Western Australia	Australia	6000
40	Prostate Cancer Institute - Southern Alberta Institute of Urology	Calgary	Alberta	Canada	T2V 1P9
41	Cross Cancer Institute	Edmonton	Alberta	Canada	AB T6G 1Z2
42	BCCA - Fraser Valley Cancer Center	Surrey	British Columbia	Canada	BC V3V 1Z2
43	BCCA Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 4E6
44	CancerCare Manitoba	Winnipeg	Manitoba	Canada
45	Horizon Health Network - Dr Everett Chalmers Hospital	Fredericton	New Brunswick	Canada	NB E3B 5N5
46	Saint John Regional Hospital	Saint John	New Brunswick	Canada	NB E2L 4L4
47	QEII Health Sciences Centre, Capital District Health Authority	Halifax	Nova Scotia	Canada	NS B3H 2Y9
48	Cambridge Memorial Hospital	Cambridge	Ontario	Canada	ON N1R 7S6
49	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
50	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	ON K7L 5P9
51	London Regional Cancer Program	London	Ontario	Canada	N6A 5W9
52	Lakeridge Health Oshawa	Oshawa	Ontario	Canada	ON L1G 2B9
53	Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	ON K1H 8L6
54	Algoma District Cancer Program Sault Area Hospital	Sault Ste. Marie	Ontario	Canada	P6B 0A8
55	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario	Canada	ON P7B 6V4
56	University Health Network - Princess Margaret Hospital	Toronto	Ontario	Canada	ON M5G 2M9
57	Hôpital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
58	CHUQ-Pavillon Hotel-Dieu de Quebec	Québec City	Quebec	Canada	QC G1R 2J6
59	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
60	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
61	Beaumont Hospital	Beaumont	Dublin	Ireland	Dublin 9
62	Beacon Private Hospital	Dublin		Ireland	Dublin 18
63	St Vincent's University Hospital	Dublin		Ireland	Dublin 4
64	Mater Misercordiae University Hospital	Dublin		Ireland	Dublin 7
65	Mater Private Hospital	Dublin		Ireland	Dublin 7
66	St James Hospital	Dublin		Ireland	Dublin 8
67	Galway University Hospital	Galway		Ireland
68	Adelaide and Meath Hospital - National Children's Hospital	Tallaght		Ireland	Dublin 24
69	University Hospital Waterford	Waterford		Ireland
70	Auckland City Hospital	Auckland		New Zealand
71	Christchurch Hospital	Christchurch		New Zealand	8140
72	Waikato Hospital	Hamilton		New Zealand	3204
73	Royal Cornwall Hospital	Truro	Cornwall	United Kingdom	TR1 3LQ
74	Royal Sussex Hospital	Brighton	East Sussex	United Kingdom	BN2 5BE
75	Kent and Canterbury Hospital	Canterbury	Kent	United Kingdom	CT1 3NG
76	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
77	Velindre Cancer Centre	Cardiff	Wales	United Kingdom	CF14 2TL
78	University College Hospital London	London		United Kingdom	NW1 2BU
79	Guys and St Thomas Hospital	London		United Kingdom	SE1 9RT
80	Royal Marsden Hospital	London		United Kingdom	SW3 6JJ
81	University Hospital Southampton	Southampton		United Kingdom	SO16 6YD
82	Great Western Hospital	Swindon		United Kingdom	SN3 6BB