Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

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). (#455)

Danka Zebic 1 , Martin R Stockler 1 2 , Andrew Martin 1 , Farzana Pashankar 3 , Ben Tran 4 5 , Danish Mazhar 6 , Robert Huddart 7 , Matthew Wheater 8 , Euan Walpole 9 , Elaine Dunwoodie 10 , Darren Feldman 11 , Alison Birtle 12 , Amanda G Stevanovic 13 , David Wyld 14 , Fritha J Hanning 15 , Peter S Grimison 1 2 5
  1. NHMRC Clinical Trials Centre, Allawah, NSW, Australia
  2. 2. Chris O'Brien Lifehouse, Sydney, NSW, Australia
  3. 3. Yale School of Medicine, New Haven, CT, USA
  4. 4. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  5. 5. Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia
  6. 6. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  7. 7. Royal Marsden Hospital, London, UK
  8. 8. University Hospital Southampton, Southampton, UK
  9. 9. Princess Alexandra Hospital, Brisbane, QLD, Australia
  10. 10. St James’s University Hospital, Leeds, UK
  11. 11. Memorial Sloan Kettering Cancer Centre, New York, USA
  12. 12. Royal Preston Hospital, Preston, UK
  13. 13. Nepean Cancer Care Centre, Kingswood, NSW, Australia
  14. 14. Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
  15. 15. Auckland City Hospital, Auckland, New Zealand

Background Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for intermediate or poor risk metastatic GCT (1). Accelerating standard regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers (2-4). P3BEP will determine effects of accelerated versus standard BEP in this setting. This is a first international, randomised trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes.

 

Methods This open label, randomised, phase 3 trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n=150) was 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 I 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-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 occur at 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour and baseline blood samples are collected for translational substudies.

 

Progress As of June 2022, 211 participants have been recruited from 23 ANZ sites, 17 UK sites (led by Cambridge Clinical Trials Unit), and 149 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n=76) identified no safety concerns. Stage I analysis (n=150) showed sufficiently favourable results with no futility concerns, supporting ongoing trial recruitment.

  1. Grimson PS, Toner GC. Management of Advanced Germ Cell Tumors: IGCCC Intermediate- and Poor-Risk Patients. In Scardino PT, Linehan WM, Zelefsky MJ et al. (eds) Comprehensive Textbook of Genitourinary Oncology, 4th edition. Philadelphia: Lippincott Williams & Wilkins 2011;594-602.
  2. Bonilla L, Ben-Aharon I, Vidal L et al. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 2010; 102:1845-1854.
  3. Pfreundschuh M, Trumper L, Kloess M et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: result of the NHL-B1 trial of the DSHNHL. Blood 2004:104; 626-633.
  4. Womer RB, West DC, Krailo MD et al. Randomised controlled trial of interval compressed chemotherapy for the treatment of localised Ewing sarcoma: a report from the Children’s Oncology Group J Clin Oncol 2012; 30: 4148-4154.