Poster Presentation COSA 2015 ASM

A randomised phase 3 trial of accelerated versus standard BEP chemotherapy for patients with intermediate and poor-risk metastatic germ cell tumours: The P3BEP Trial (ANZUP 1302) (#266)

Nicola Lawrence 1 , Guy Toner 2 , Andrew Martin 1 , Martin Stockler 1 , Annie Yeung 1 , Nicole Wong 1 , Damien Thomson 3 , Val Gebski 1 , Sonia Yip 1 4 , Madeleine King 5 , Michael Friedlander 6 , David Quinn 7 , Thean Hsiang Tan 8 , Howard Chan 1 , Fritha Hanning 9 , Andrew Weickhardt 10 , Mark Jeffery 11 , Amanda Stevanovic 12 , Elizabeth Hovey 13 , David Wyld 14 , Ian Davis 15 , Peter Grimison 16 , and on behalf of ANZUP 17
  1. NHMRC Clinical Trials Group, Camperdown, NSW, Australia
  2. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  3. Princess Alexandra Hospital, Brisbane, Queensland, Australia
  4. Sydney Catalyst Translational Cancer Research Centre, Sydney, NSW, Australia
  5. School of Psychology and Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  6. Prince of Wales Hospital, Sydney, NSW, Australia
  7. University of Southern California , Los Angeles, California , United States of America
  8. Royal Adelaide Hospital, Adelaide, SA
  9. Auckland Hospital, Auckland, New Zealand
  10. Austin Health, Melbourne, Victoria, Australia
  11. Christchurch Hospital, Christchurch, New Zealand
  12. Nepean Hospital, Sydney, NSW, Australia
  13. Prince of Wales Hospital, Sydney, NSW, Australia
  14. Royal Brisbane and Women's Hospital, Brisbane, Australia
  15. Monash University Eastern Health Clinical School, Melbourne, Victoria , Australia
  16. Chris O'Brien Lifehouse, Sydney, NSW, Australia
  17. Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia

Background: Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for intermediate- and poor-risk metastatic germ cell tumours (GCTs). High-dose chemotherapy and more complex regimens (eg VIP, T-BEP) have failed to improve cure rates. Accelerating regimens of standard chemotherapy by administering them 2-weekly rather than 3-weekly has improved cure rates in other cancers.

Aim: To determine if accelerated BEP is superior to standard BEP as 1st line chemotherapy for intermediate and poor-risk metastatic GCTs.

Design: Open-label, randomised, stratified 2-arm multicentre, 2 stage, phase 3 clinical trial. Primary endpoint: for stage I of the trial (n=150) is complete response rate, and for complete trial (n=500) is progression-free survival (PFS). Sample size: 150 and 500 patients gives >80% power to detect a 20% improvement in response rates and 7% absolute improvement in 2yr PFS, respectively.

Participants: Males aged 16-45 years with intermediate or poor-risk metastatic GCTs for 1st line chemotherapy. Planned expansion to include children aged 11+ and females.

Regimen: Randomisation 1:1 to “standard BEP” or “accelerated BEP” comprising 4 cycles of: cisplatin 20mg/m2 IV days 1-5; etoposide 100mg/m2 IV days 1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF 6mg SC on Day 6; given every 3 weeks or every 2 weeks respectively. In the accelerated BEP arm 4 additional weekly doses of bleomycin follow.

Assessments: Initial response assessment at 30-day safety assessment. Final response assessment at 6 months from randomisation or after all post-chemotherapy intervention is completed. Follow-up (including patient-reported outcomes) 3-monthly for 2 years from randomisation, then 6-monthly to 5 years, then annually. Archival tumour tissue and baseline bloods for future translational substudies will be collected.

Status: 27/29 sites open in ANZ by August 2015, 17 patients recruited. International collaborations with Ireland and UK confirmed with sites expected to open by late 2015, additional collaborations with paediatric and adult groups in USA planned.

Co-funded by Cancer Council Australia and Cancer Australia. ANZUP supported by Cancer Australia and CINSW. ANZCTR:ACTRN12613000496718