Poster Presentation COSA 2015 ASM

Randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate  cancer: ENZARAD (ANZUP 1303) (#273)

Scott G Williams 1 , Ian D Davis 2 , Christopher Sweeney 3 , Martin R Stockler 4 , Andrew Martin 4 , Wendy Hague 4 , Xanthi Coskinas 4 , Anne Long 4 , Sonia Yip 4 5 , Emily Tu 4 , Howard Chan 4 , Nicky Lawrence 4 , Ray McDermott 6 , Simon Hughes 7 , Vittorio Marchesin 6 , Olwyn Deignan 6 , Paul L Nguyen 3
  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. Monash University Eastern Health Clinical School, Melbourne, Victoria , Australia
  3. Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
  4. NHMRC Clinical Trials Group, Camperdown, NSW, Australia
  5. Sydney Catalyst Translational Cancer Research Centre, Sydney, NSW, Australia
  6. All-Ireland Co-operative Oncology Research Group (ICORG), Dublin, Ireland
  7. Guys and St Thomas' NHS Foundation Trust , London, United Kingdom

Background:Adjuvant androgen deprivation therapy (ADT)  with luteinising hormone releasing hormone analogue (LHRHA) is standard of care given before during and after radiotherapy for localised prostate cancer (PC) at risk of recurrence. Enzalutamide is a second generation androgen receptor (AR) inhibitor with a higher affinity to the AR than conventional non-steroidal anti-androgens (NSAA).Enzalutamide improves survival in metastatic castration-resistant PC. We hypothesize the addition of enzalutamide in adjuvant ADT, given before, during and after radiation therapy for localised PCat high risk of recurrence, will improve outcomes.

Aim:To determine the effectiveness of enzalutamide as part of adjuvant ADT with LHRHA in men planned for radiotherapy for localised PC at high risk of recurrence.

Trial Design:Open label, randomised, stratified, 2-arm multicentre, phase 3 trial. Primary endpoint is OS, secondary endpoints:  cause-specific survival, PSA PFS, clinical PFS, time to subsequent hormonal therapy, time to castration-resistant disease (PCWG2 criteria), metastasis free survival, adverse events and HRQOL. Target accrual: 800 participants. 2 yrs accrual + 5.5 years minimum f/up. 80% power to detect  33% reduction in the hazard of death assuming 5-year survival rate of 76% amongst controls.

Treatment: LHRHA for 24 months and EBRT (78Gy/39F) starting after week 16 for all participants and randomised 1:1 to enzalutamide 160mg daily for 24 months versus conventional NSAA for first 6 months. 

Assessments: Baseline, weeks 4, 12,16, 20 and 24, then 3-4 monthly until year 5, 6-monthly until year 7, then annually. CT/MRI and bone scan at baseline, PSA progression, 6 monthly until re-initiation of ADT and 3 monthly until evidence of metastases. Tertiary c objectives are identification of prognostic/predictive biomarkers from archival tumour tissue, and fasting research bloods at 4 different time points.

Status: As of August 2015, 35sites open in Australia, New Zealand, Ireland and US

Enzarad is an investigator initiated cooperative group trial financed by Astellas. ANZUP is supported by Cancer Australia and CI NSW

ClinicalTrials.gov: NCT02446444, ANZCTR: ACTRN12614000126617