e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for male and female adults and children with intermediate and poor-risk metastatic germ cell tumours (GCTs). (#413)

Shalini Subramaniam 1 2 , Guy C Toner 2 3 , Martin R Stockler 1 2 4 , Andrew Martin 1 , Farzana Pashankar 5 , Ben Tran 2 3 , Mark Jeffery 6 , Danish Mazhar 7 , Robert Huddart 8 , Euan Walpole 9 , Amanda G Stevanovic 10 , David Wyld 11 , Fritha J Hanning 12 , Matthew Wheater 13 , Jay M Balagtas 14 , Simon Troon 15 , Alison Birtle 16 , Jeffery White 17 , Peter S Grimison 1 2 4
  1. NHMRC Clinical Trials Centre, Camperdown, NSW, Australia
  2. Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia
  3. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  4. Chris O'Brien Lifehouse, Sydney, NSW, Australia
  5. Yale School of Medicine, New Haven, Connecticut, USA
  6. Christchurch Hospital, Christchurch, New Zealand
  7. Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
  8. Royal Marsden Hospital, London, United Kingdom
  9. Princess Alexandra Hospital, Brisbane, QLD, Australia
  10. Nepean Cancer Care Centre, Kingswood, NSW, Australia
  11. Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
  12. Auckland City Hospital, Auckland, New Zealand
  13. University Hospital Southampton, Southampton, United Kingdom
  14. Lucile Packard Children’s Hospital Stanford, Palo Alto, California, USA
  15. Fiona Stanley Hospital, Murdoch, WA, Australia
  16. Royal Preston Hospital, Preston, United Kingdom
  17. Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom

Background Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 is standard 1st line chemotherapy for metastatic GCT categorised as intermediate risk or poor risk. Acceleration of standard regimens by shortening the cycle length improved cure rates in other cancers. We aim to determine the superiority of accelerated BEP versus standard BEP in this setting.

Methods This open label, randomised, phase 3 trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n=150) is complete response (CR); and for stage 2 (n=500) is progression free survival at 2 years (PFS2y). These sample sizes provide >80% power with a two-sided type error rate of 5% to detect an absolute improvement of 25% in the CR rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate-risk or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomised (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily. Study assessments 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour tissue and baseline blood samples are collected for translational substudies. As of August 2020, 135 participants have been recruited from 25 ANZ sites, 14 UK sites (led by Cambridge Clinical Trials Unit), and 140 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n=76) identified no safety concerns. The stage I analysis is anticipated mid-2021.

This international randomised trial of chemotherapy for intermediate and poor-risk metastatic GCT is the first to include adults and children of both sexes..

ClinicalTrials.gov: NCT02582697