Randomised phase 3 trial of enzalutamide in first line androgen deprivation therapy for metastatic prostate cancer: the ANZUP ENZAMET Trial (ANZUP 1304) — ASN Events
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  3. Randomised phase 3 trial of enzalutamide in first line androgen deprivation therapy for metastatic prostate cancer: the ANZUP ENZAMET Trial (ANZUP 1304)

Randomised phase 3 trial of enzalutamide in first line androgen deprivation therapy for metastatic prostate cancer: the ANZUP ENZAMET Trial (ANZUP 1304) (#269)

Ian Davis 1 , Martin Stockler 2 , Andrew Martin 2 , Wendy Hague 2 , Xanthi Coskinas 2 , Sonia Yip 2 3 , Carlo Dazo 2 , Anne Long 2 , Nicky Lawrence 2 , Howard Chan 2 , Ray McDermott 4 , Simon Chowdhury 5 , Vittorio Marchesin 4 , Olwyn Deignan 4 , Wendy Parulekar 6 , Alexander Montenegro Suris 6 , Christopher Sweeney 7 , and on behalf of ANZUP 8
  1. Monash University Eastern Health Clinical School, Melbourne, Victoria , Australia
  2. NHMRC Clinical Trials Group, Camperdown, NSW, Australia
  3. Sydney Catalyst Translational Cancer Research Centre, Sydney, NSW, Australia
  4. All-Ireland Co-operative Oncology Research Group (ICORG), Dublin, Ireland
  5. Guys & St Thomas NHS Trust, Kings College , London, United Kingdown
  6. NCIC, Clinical Trials Group, Kingston, Ontario, Canada
  7. Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
  8. Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia

Background: Androgen deprivation therapy (ADT) with a luteinising hormone releasing hormone analogue (LHRHA) or surgical castration, either alone or in combination with conventional non-steroidal anti-androgen (NSAA), is widely used as initial treatment for hormone-naive, metastatic prostate cancer. Meta-analysis of RCTs showed a 3% absolute improvement in 5 year survival with the addition of NSAA to ADT. Residual, low level androgen receptor (AR) signalling or agonist activity from conventional NSAA may provide a stimulatory signal to hormone-sensitive prostate cancer cells. We hypothesize that the early use of enzalutamide, a more potent and effective androgen receptor blocker, will reduce residual AR signalling, and improve survival. The aim is to determine the effectiveness of ADT + enzalutamide versus ADT + conventional NSAA, as 1st line endocrine therapy for metastatic prostate cancer.

Methods: Design: open label, randomised, stratified, 2-arm, intergroup, phase 3 trial including ANZ, Canada, UK, Ireland and USA. Eligibility: metastatic prostate cancer starting 1st line ADT. Stratification: volume of disease, anti-resorptive therapy, comorbidities, early docetaxel use, study site. Endpoints: overall survival (primary), PSA progression free survival (PFS), clinical PFS, health related quality of life, adverse events and cost-effectiveness. 1100 target participants recruited over 2 years + 3.5 years minimum follow-up for 80% power to detect a 25% reduction in the hazard of death assuming an OS rate at 3 years of 65% in control group. Treatment: LHRHA or surgical castration plus either enzalutamide 160mg daily orally, or conventional oral NSAA until disease progression or prohibitive toxicity. Assessments: baseline, days 29 and 85 then 12 weekly until clinical progression; imaging prior to randomisation and on progression (PSA and clinical). Tertiary correlative objectives: identification of prognostic/predictive biomarkers from archival tumour tissue and fasting bloods collected at baseline, week 24 and progression (PSA and clinical). 55 sites open with total accrual of 235 participants on 4th August 2015.

ENZAMET is an investigator-initiated cooperative group trial funded by Astellas. ANZUP is supported by Cancer Australia and CINSW.

ClinicalTrials.gov Identifier:NCT02446405, ANZCTR:ACTRN12614000110684

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