P3BEP (ANZUP 1302): An international randomised phase III trial of accelerated versus standard bep chemotherapy for adult and pediatricmale and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTS)

Abstract

Background: Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard first-line chemotherapy for intermediate and poor-risk metastaticGCTs. High-dose chemotherapy and more complex regimens (e.g. 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 first-line chemotherapy for intermediate and poor-risk metastatic GCTs. Design: Open-label, randomised, stratified, two-arm multicentre, twostage, phase-III 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 of 150 and 500 patients gives >80% power to detect a 20% improvement in response-rate and 7% absolute improvement in 2-year PFS, respectively. Participants: Male and female participants aged 11-45 years with intermediate or poor-risk metastatic GCTs of testis, ovary, retroperitoneum andmediastinum for first-line chemotherapy. Regimen: Randomisation 1:1 to “standard BEP” or “accelerated BEP” comprising four cycles of: cisplatin 20 mg/m2 IV days 1-5; etoposide 100 mg/m2 IV days 1-5; bleomycin IV weekly; and pegylated G-CSF or filgrastim; 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 safetyassessment. Final response assessment at 6 months from randomisation or after all post-chemotherapy intervention is completed. Follow-up 3-monthly for 24-months from randomisation, then 6-monthly for 24-60 months, then annually. Archival tumour-tissue and bloods will be collected for future translational substudies. Status: Twenty-five sites open in ANZ by August 2017, 40 patients recruited. One of 19 sites open in UK by August 2017. International collaborations with Ireland and USA (children and adult groups) confirmed with sites expected to open by late 2017.L6193512592017-11-27 <br />